Tesis: "Interactive molecular simulations"

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Ashe, Colin Alexander. "Interactive online simulations and curriculum for teaching and learning fundamental concepts in molecular science at the undergraduate level". Thesis, Massachusetts Institute of Technology, 2010. http://hdl.handle.net/1721.1/59212.

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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2010.
Includes bibliographical references (p. 213-218).
The number of research disciplines that focus, at least in part, on the atomic or molecular level is rapidly increasing. As a result, the concepts that describe the behavior of atoms and molecules, known collectively as "Molecular Science", are becoming an educational necessity for an expanding fraction of college and university students. Unfortunately, these concepts are challenging for students to learn. Because of the growing importance of these concepts and their difficulty, a project was undertaken with the goal of helping students to understand these concepts using simplified, interactive models. Students in their first year of undergraduate study were targeted. The primary goal of the project was to help students understand the so-called "energy landscape", also known as the "potential energy surface". This concept is central to Molecular Science because it contains information about both equilibrium and kinetic properties of a system. It is also widely used in textbooks and by experts for reasoning qualitatively. Interactive simulations, along with related curriculum, were created in order to help students understand the energy landscape and explore its implications. The simulations visualize simplified models, which were chosen for their analogic connection to chemical systems as well as their similarity to things with which students could intuitively relate. The primary models used were two- and three-dimensional cardboard boxes, as well as a series of platforms covered with balls. The models were simulated and visualized in Java applets. Curriculum sequences consisting of applets, exercises, and explanations were carefully constructed to present concepts in a logical order. The materials were made available online at MatDL.org, the materials pathway of the National Science Digital Library. The curriculum sequences were used as a supplemental exercise by students at Kent State University, Carnegie Mellon University (CMU), and the Massachusetts Institute of Technology (MIT). Two large assessments of student learning were conducted: one at CMU and one at MIT, involving over 400 total students. Assessment results demonstrated that using the project materials improved students' performance on the assessment tests with a greater than 99.9% degree of confidence. Free response comments indicated that students found the exercises helpful and interesting.
by Colin Alexander Ashe.
Ph.D.

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2

Lanrezac, André. "Interprétation de données expérimentales par simulation et visualisation moléculaire interactive". Electronic Thesis or Diss., Université Paris Cité, 2023. http://www.theses.fr/2023UNIP7133.

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L'objectif de l'approche des simulations moléculaires interactive (Interactive Molecular Simulations - IMS) est d'observer en direct la dynamique conformationnelle d'une simulation moléculaire en cours. Le retour visuel instantané permet un suivi instructif ainsi que l'observation des changements structurels imposés par la manipulation de l'IMS par l'utilisateur. J'ai mené une étude approfondie des connaissances pour rassembler et synthétiser l'ensemble des recherches qui ont développé l'IMS. La dynamique moléculaire interactive (Interactive Molecular Dynamics - IMD) est l'un des premiers protocoles IMS qui a posé les bases du développement de cette approche. Mon laboratoire de thèse s'est inspirée de celle-ci pour développer le moteur de simulation BioSpring basé sur le modèle de réseaux élastique. Ce modèle permet de simuler la flexibilité de grands ensembles biomoléculaires et ainsi potentiellement révéler des changements à longue échelle de temps qui ne seraient pas facilement saisis par la dynamique moléculaire. Ce moteur de simulation ainsi que le logiciel de visualisation UnityMol, développé par le biais du moteur de jeu Unity3D, et liés par l'interface de communication MDDriver ont été étendus pour les faire converger vers une suite logicielle complète. Le but est de fournir à un expérimentateur, qu'il soit expert ou profane, une boîte à outils complète pour modéliser, afficher et contrôler interactivement l'ensemble des paramètres d'une simulation. L'implémentation particulière d'un tel protocole, basé sur une communication formalisée et extensible entre les différents composants, a été pensée pour pouvoir facilement intégrer de nouvelles possibilités de manipulation interactive et des jeux de données expérimentales qui s'ajouteront aux contraintes imposées à la simulation. L'utilisateur peut donc manipuler la molécule d'intérêt sous le contrôle des propriétés biophysiques intégrés dans le modèle simulé, tout en ayant la possibilité de piloter à la volée les paramètres de simulation. Aussi, un des objectifs initiaux de cette thèse était d'intégrer la gestion des contraintes d'interaction ambigües du logiciel d'amarrage biomoléculaire HADDOCK directement dans UnityMol, rendant possible l'utilisation de ces mêmes contraintes à une variété de moteurs de simulations. Un axe principal de ces recherches était de développer un algorithme de positionnement rapide et interactif de protéines dans des membranes implicite tiré d'un modèle appelé Integrative Membrane Protein and Lipid Association Method (IMPALA) développée par l'équipe de Robert Brasseur en 1998. La première étape consistait à effectuer une recherche approfondie des conditions dans lesquelles les expériences ont été réalisées à l'époque, afin de vérifier la méthode et de valider notre propre implémentation. Nous verrons qu'elle ouvre des questions intéressantes sur la manière dont on peut reproduire les expériences scientifiques. L'étape finale qui conclue cette thèse était le développement d'une nouvelle méthode universelle d'interaction lipide-protéine, UNILIPID, qui est un modèle d'incorporation interactif de protéines dans les membranes implicites. Elle est indépendante de l'échelle de représentation, peut être appliquée à des niveaux tout atomes, gros-grains jusqu'au niveau d'un grain par acide aminé. La représentation de la dernière version Martini3[6] ainsi qu'une méthode d'échantillonnage Monte-Carlo et de simulation de dynamique des corps rigides ont été spécialement intégrés à la méthode, en plus de divers outils de préparation de systèmes. En outre, UNILIPID est une approche versatile qui reproduit précisément des termes d'hydrophobicité expérimentaux pour chaque acide aminé. En plus de membranes implicites simples, je décrirai une implémentation analytique de membranes doubles ainsi qu'une généralisation à des membranes de forme arbitraire, toutes deux s'appuyant sur des applications inédites
The goal of Interactive Molecular Simulations (IMS) is to observe the conformational dynamics of a molecular simulation in real-time. Instant visual feedback enables informative monitoring and observation of structural changes imposed by the user's manipulation of the IMS. I conducted an in-depth study of knowledge to gather and synthesize all the research that has developed IMS. Interactive Molecular Dynamics (IMD) is one of the first IMS protocols that laid the foundation for the development of this approach. My thesis laboratory was inspired by IMD to develop the BioSpring simulation engine based on the elastic network model. This model allows for the simulation of the flexibility of large biomolecular ensembles, potentially revealing long-timescale changes that would not be easily captured by molecular dynamics. This simulation engine, along with the UnityMol visualization software, developed through the Unity3D game engine, and linked by the MDDriver communication interface, has been extended to converge towards a complete software suite. The goal is to provide an experimenter, whether an expert or novice, with a complete toolbox for modeling, displaying, and interactively controlling all parameters of a simulation. The particular implementation of such a protocol, based on formalized and extensible communication between the different components, was designed to easily integrate new possibilities for interactive manipulation and sets of experimental data that will be added to the restraints imposed on the simulation. Therefore, the user can manipulate the molecule of interest under the control of biophysical properties integrated into the simulated model, while also having the ability to dynamically adjust simulation parameters. Furthermore, one of the initial objectives of this thesis was to integrate the management of ambiguous interaction constraints from the HADDOCK biomolecular docking software directly into UnityMol, making it possible to use these same restraints with a variety of simulation engines. A primary focus of this research was to develop a fast and interactive protein positioning algorithm in implicit membranes using a model called the Integrative Membrane Protein and Lipid Association Method (IMPALA), developed by Robert Brasseur's team in 1998. The first step was to conduct an in-depth search of the conditions under which the experiments were performed at the time to verify the method and validate our own implementation. We will see that this opens up interesting questions about how scientific experiments can be reproduced. The final step that concluded this thesis was the development of a new universal lipid-protein interaction method, UNILIPID, which is an interactive protein incorporation model in implicit membranes. It is independent of the representation scale and can be applied at the all-atom, coarse-grain, or grain-by-grain level. The latest Martini3 representation, as well as a Monte Carlo sampling method and rigid body dynamics simulation, have been specially integrated into the method, in addition to various system preparation tools. Furthermore, UNILIPID is a versatile approach that precisely reproduces experimental hydrophobicity terms for each amino acid. In addition to simple implicit membranes, I will describe an analytical implementation of double membranes as well as a generalization to arbitrarily shaped membranes, both of which rely on novel applications

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Cardona, Amengual Javier. "Molecular simulations of the interaction of microwaves with fluids". Thesis, University of Strathclyde, 2016. http://digitool.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=27631.

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The interaction of electromagnetic radiation with matter has led to a large number of interesting applications. The propagation of electromagnetic waves within materials is described by Maxwell’s equations. However, the fundamental understanding of the causes of the response of the material, defined by constitutive relations for its complex, frequency-dependent dielectric constant, can only be achieved through the study of processes occurring at the molecular scale. The fluctuation-dissipation theorem relates the frequency-dependent dielectric constant of a material to equilibrium fluctuations in its dipole moment. This fact can be used to determine dielectric properties from equilibrium molecular dynamics simulations for frequencies covering the microwave region of the electromagnetic spectrum (300 MHz – 300 GHz). In this work, the ability of current force fields to predict dielectric spectra of one component systems and mixtures is examined, showing accurate results when compared with experimental data for the systems under consideration. Additionally, the influence of temperature on the dielectric spectra is analysed, yielding equally satisfactory results. In the particular case of ethanol/water mixtures, the estimation of dielectric spectra at intermediate concentrations using molecular dynamics simulations outperforms the traditional use of mixing rules. The simulations of these systems reveal the importance of collaborative processes between groups of molecules, such as hydrogen bond networks, in the overall dielectric response. The reduction of the contribution of these processes as temperature increases confirms the weakening of these networks at high temperatures. The predicted dielectric properties are used in a heating model to estimate temperature profiles in microwave heating processes. Unexpected results are obtained which reveal the need for accurate determination of the electric field distribution within the workload in order to obtain representative heating profiles. In contrast, penetration depths are accurately determined from dielectric properties generated through molecular simulations.

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Bryson, Kevin. "Molecular simulation of DNA and its interaction with polyamines". Thesis, University of York, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.297070.

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França, João. "Solid-liquid interaction in ionanofluids. Experiments and molecular simulation". Thesis, Université Clermont Auvergne‎ (2017-2020), 2017. http://www.theses.fr/2017CLFAC077.

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L'un des principaux domaines de recherche en chimie et en ingénierie chimique implique l'utilisation de liquides ioniques et de nanomatériaux comme alternatives à de nombreux produits chimiques et processus chimiques, comme ce dernier étant actuellement considérés comme non respectueux de l'environnement. Leur utilisation potentiel comme nouveaux fluides de transfert de chaleur et matériaux de stockage de chaleur, qui peuvent obéir à la plupart des principes de la chimie verte, nécessite l'étude expérimentale et théorique des mécanismes de transfert de chaleur dans les fluides complexes comme les ionanofluides. Le but de cette thèse était d'étudier les ionanofluides, qui consistent en la dispersion de nanomatériaux dans un liquide ionique.Le premier objectif de ce travail était de mesurer les propriétés thermophysiques des liquides ioniques et ionanofluides, à savoir la conductivité thermique, la viscosité, la densité et la capacité thermique dans une gamme de température comprise entre -10 et 150 ºC et à pression atmosphérique. Dans ce sens, les propriétés thermophysiques d'un ensemble considérable de liquides ioniques et d'ionanofluides ont été mesurées, avec un accent particulier sur la conductivité thermique des fluides. Les liquides ioniques étudiés étaient [C2mim][EtSO4], [C4mim][(CF3SO2)2N], [C2mim][N(CN)2], [C4mim][N(CN)2], [C4mpyr][N(CN)2], [C2mim][SCN], [C4mim][SCN], [C2mim][C(CN)3], [C4mim][C(CN)3], [P66614][N(CN)2], [P66614][Br] et leurs suspensions avec 0.5% et 1% w/w de nanotubes de carbone multi-parois (MWCNTs - de l'anglais multi-walled carbon nanotubes). Les résultats obtenus montrent qu'il y a une augmentation substantielle de la conductivité thermique du fluide de base due à la suspension du nanomatériau, en considérant les deux fractions massiques. Cependant, l'amélioration varie de manière significative lorsqu'on considère différents liquides ioniques de base, avec une gamme comprise entre 2 et 30%, avec une température croissante. Ce fait rend plus difficile l'unification des informations obtenues afin d'obtenir un modèle permettant de prédire l'amélioration de la conductivité thermique. Les modèles actuellement utilisé pour calculer la conductivité thermique des nanofluides présentent des valeurs considérablement sous-estimées par rapport aux valeurs expérimentales, en partie à cause des considérations sur le rôle de l'interface solide-liquide sur le transport de la chaleur.En ce qui concerne la densité, l'impact de l'ajout de MWCNTs sur la densité du fluide de base est très faible, variant entre 0.25% et 0.5% pour 0.5% w/w et 1% w/w MWCNTs, respectivement. Cela était assez attendu et est dû à la différence considérable de densité entre les deux types de matériaux. Cependant, la viscosité était la propriété pour laquelle les valeurs les plus élevées d' augmentation ont été vérifiées, allant de 28 à 245% pour les deux fractions massiques de MWCNT. La capacité calorifique était la seule des quatre propriétés mentionnées ci-dessus à ne pas être étudiée dans ce travail en raison de problèmes techniques avec le calorimètre à utiliser. Néanmoins, la quantité de données recueillies sur les propriétés thermophysiques restantes était extensif. On pense que ce dernier contribue de manière significative à une base de données croissante des propriétés des liquides ioniques et des ionanofluides, tandis que en fournissant un aperçu de la variation des propriétés obtenues à partir de la suspension de MWCNTs dans des liquides ioniques.(...)
One of the main areas of research in chemistry and chemical engineering involves the use of ionic liquids and nanomaterials as alternatives to many chemical products and chemical processes, as the latter are currently considered to be environmentally non-friendly. Their possible use as new heat transfer fluids and heat storage materials, which can obey to most principles of green chemistry or green processing, requires the experimental and theoretical study of the heat transfer mechanisms in complex fluids, like the ionanofluids. It was the purpose of this dissertation to study ionanofluids, which consist on the dispersion of nanomaterials in an ionic liquid.The first objective of this work was to measure thermophysical properties of ionic liquids and ionanofluids, namely thermal conductivity, viscosity, density and heat capacity in a temperature range between -10 e 150 ºC and at atmospherical pressure. In this sense, the thermophysical properties of a considerable set of ionic liquids and ionanofluids were measured, with particular emphasis on the thermal conductivity of the fluids. The ionic liquids studied were [C2mim][EtSO4], [C4mim][(CF3SO2)2N], [C2mim][N(CN)2], [C4mim][N(CN)2], [C4mpyr][N(CN)2], [C2mim][SCN], [C4mim][SCN], [C2mim][C(CN)3], [C4mim][C(CN)3], [P66614][N(CN)2], [P66614][Br] and their suspensions with 0.5% and 1% w/w of multi-walled carbon nanotubes (MWCNTs). The results obtained show that there is a substantial enhancement of the thermal conductivity of the base fluid due to the suspension of the nanomaterial, considering both mass fractions. However, the enhancement varies significantly when considering different base ionic liquids, with a range between 2 to 30%, with increasing temperature. This fact makes it more difficult to unify the obtained information in order to obtain a model that allows predicting the enhancement of the thermal conductivity. Current models used to calculate the thermal conductivity of nanofluids present values that are considerably underestimated when compared to the experimental ones, somewhat due to the considerations on the role of the solid-liquid interface on heat transport.Considering density, the impact from the addition of MWCNTs on the base fluid’s density is very low, ranging between 0.25% and 0.5% for 0.5% w/w and 1% w/w MWCNTs, respectively. This was fairly expected and is due to the considerable difference in density between both types of materials. However, viscosity was the property for which the highest values of enhancement were verified, ranging between 28 and 245% in both mass fractions of MWCNTs. The heat capacity was the only of the four properties mentioned above not to be studied in this work due to technical issues with the calorimeter to be used. Nevertheless, the amount of data collected on the remainder thermophysical properties was extensive. It is believed that the latter contributes meaningfully to a growing database of ionic liquids and ionanofluids’ properties, while providing insight on the variation of said properties obtained from the suspension of MWCNTs in ionic liquids.The second objective of this work consisted on the development of molecular interaction models between ionic liquids and highly conductive nanomaterials, such as carbon nanotubes and graphene sheets. These models were constructed based on quantum calculations of the interaction energy between the ions and a cluster, providing interaction potentials. Once these models were obtained, a second stage on this computational approach entailed to simulate, by Molecular Dynamics methods, the interface nanomaterial/ionic liquid, in order to understand the specific interparticle/molecular interactions and their contribution to the heat transfer. This would allow to study both structural properties, such as the ordering of the ionic fluid at the interface, and dynamic ones, such as residence times and diffusion. (...)

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Gacek, Sobieslaw Stanislaw. "Molecular dynamics simulation of shock waves in laser-material interaction". [Ames, Iowa : Iowa State University], 2009.

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7

Hedman, Fredrik. "Algorithms for Molecular Dynamics Simulations". Doctoral thesis, Stockholm University, Department of Physical, Inorganic and Structural Chemistry, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-1008.

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Methods for performing large-scale parallel Molecular Dynamics(MD) simulations are investigated. A perspective on the field of parallel MD simulations is given. Hardware and software aspects are characterized and the interplay between the two is briefly discussed.

A method for performing ab initio MD is described; the method essentially recomputes the interaction potential at each time-step. It has been tested on a system of liquid water by comparing results with other simulation methods and experimental results. Different strategies for parallelization are explored.

Furthermore, data-parallel methods for short-range and long-range interactions on massively parallel platforms are described and compared.

Next, a method for treating electrostatic interactions in MD simulations is developed. It combines the traditional Ewald summation technique with the nonuniform Fast Fourier transform---ENUF for short. The method scales as N log N, where N is the number of charges in the system. ENUF has a behavior very similar to Ewald summation and can be easily and efficiently implemented in existing simulation programs.

Finally, an outlook is given and some directions for further developments are suggested.

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Marchi, Davide. "Multiscale modelling of organic molecules interacting with solids". Doctoral thesis, Università del Piemonte Orientale, 2022. http://hdl.handle.net/11579/144038.

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This Ph.D. thesis concerns the application of computational chemistry methods to molecular systems of interest, in collaboration with experimental research groups. The bulk of the work was focused on self-assembled monolayers (SAM) of thiol molecules on gold surfaces. SAMs are of central interest in surface science; they are studied for potential applications, among others, in nanolithography, biosensing, and electronics. The nature of the sulfur/gold interface is still debated: although it is commonly held that the –SH moiety dissociates to form a covalent S-Au bond, several studies report SAMs of undissociated thiols. To get insights on this point, we combined density functional theory (DFT) and molecular dynamics (MD) simulations to study in detail the thermodynamics of SAM formation on gold surfaces, using 7-mercapto-4-methylcoumarin (MMC) and 3-mercaptopropionic acid (MPA) as model molecules. The chemical potential of a thiol molecule in the SAM was computed by MD thermodynamic integration as a function of the SAM density; the maximum SAM densities for MMC and MPA in dissociated and undissociated form were computed and compared with experimental results.

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Hermansson, Anders. "Calculating Ligand-Protein Binding Energies from Molecular Dynamics Simulations". Thesis, KTH, Skolan för kemivetenskap (CHE), 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-170722.

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Indications that existing parameter sets of extended Linear Interaction Energy (LIE) models are transferable between lipases from Rhizomucor Miehei and Thermomyces Lanigunosus in complex with a small set of vinyl esters are demonstrated. By calculat- ing energy terms that represents the cost of forming cavities filled by the ligand and the complex we can add them to a LIE model with en established parameter set. The levels of precision attained will be comparable to those of an optimal fit. It is also demonstrated that the Molecular Mechanics/Poisson Boltzmann Surface Area (MM/PBSA) and Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) methods are in- applicable to the problem of calculating absolute binding energies, even when the largest source of variance has been reduced.

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Gehrcke, Jan-Philip. "Investigation of the interleukin-10-GAG interaction using molecular simulation methods". Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-163205.

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Glycosaminoglycans (GAGs) are linear polysaccharides, built of periodically occurring disaccharide units. GAGs are ubiquitous in the extracellular matrix (ECM), where they exhibit multifarious biological activities. This diversity arises from - among others - their ability to interact with and regulate a large number of proteins, such as cytokines, chemokines, and growth factors. As of the huge variety in their chemical configuration, GAGs are further sub-classified into different types (heparin, for instance, is one of these sub-classes). Hence, GAGs are a diverse class of molecules, which surely contributes to the broadness of their spectrum of biological functions. Through varying arrangements of sulfate groups and different types of saccharide units, individual GAG molecules can establish specific atomic contacts to proteins. One of the best-studied examples is antithrombin-heparin, whose biologically relevant interaction requires a specific pentasaccharide sequence. It is valid to assume, however, that various proteins are yet to be discovered whose biological functions are in some way affected by GAGs. In other cases, and this is true for the cytokine interleukin-10 (IL-10), there are already experimental indications for a biologically relevant protein-GAG interaction, but the details are still obscure and the fundamental molecular interaction mechanism has still not been clarified. IL-10 has been shown to bind GAGs. So far, however, no structural detail about IL-10-GAG interaction is known. Function-wise, IL-10 is mainly considered to be immunosuppressive and therefore anti-inflammatory, but it in fact has the pleiotropic ability to influence the immune system in both directions, i.e. it constitutes a complex regulation system on its own. Therefore, the role of GAGs in this system is potentially substantial, but is yet to be clarified. In vitro experiments have yielded indications for GAGs being able to modulate IL-10\'s biological function, and obviously IL-10 and GAGs are simultaneously present in the ECM. This gives rise to the assumption that IL-10-GAG interaction is of biological significance, and that understanding the impact of GAGs on IL-10 biology is important - from the basic research point of view, but also for the development of therapies, potentially involving artificially designed ECMs. A promising approach for obtaining knowledge about the nature of IL-10-GAG interaction is its investigation on the structural level, i.e. the identification and characterization of the molecular interaction mechanisms that govern the IL-10-GAG system. In this PhD project it was my goal to reveal structural and molecular details about IL-10-GAG interaction with theoretical and computational means, and with the help of experiments performed by collaborators in the framework of the Collaborative Research Centre DFG Transregio 67. For achieving this, I developed three methods for the in silico investigation of protein-GAG systems in general and subsequently applied them to the IL-10-GAG system. Parts of that work have been published in scientific journals, as outlined further below. I proposed and validated a systematic approach for predicting GAG binding regions on a given protein, based on the numerical simulation and analysis of its Coulomb potential. One advantage of this method is its intrinsic ability to provide clues about the reliability of the resulting prediction. Application of this approach to IL-10 lead to the observation that its Coulomb attraction for GAGs is significantly weaker than in case of exemplary protein-GAG systems (such as FGF2-heparin). Still, a distinct IL-10-GAG binding region centered on the residues R102, R104, R106, R107 of the human IL-10 sequence was identified. This region can be assumed to play a major role in IL-10-GAG interaction, as described in chapter 3. Molecular docking methods are used to generate binding mode predictions for a given receptor-ligand system. In chapter 4, I clarify the importance of data clustering as an essential step for post-processing docking results and present a clustering methodology optimized for GAG molecules. It allows for a reproducible analysis, enabling systematic comparisons among different docking studies. The approach has become standard procedure in our research group. It has been applied in a variety of studies, and served as an essential tool for studying IL-10-GAG interaction, as described in chapter 3. Motivated by the shortcomings of classical docking approaches, especially with respect to protein-GAG systems, I worked on the development of a molecular dynamics-based docking method with less radical approximations than usually applied in classical docking. The goal was to make the computational model properly account for the special physical properties of GAGs, and to include the effects of receptor flexibility and solvation. The methodology was named Dynamic Molecular Docking (DMD) and published in the Journal of Chemical Information and Modeling-together with a validation study. The subsequent application of DMD in a variety of studies required enormous amounts of computational resources. For tackling this challenge, I established a graphics processing unit-based high-performance computing environment in our research group and developed a software framework for reliably performing DMD studies on this hardware, as well as on other computing resources of the TU Dresden. The investigation of the IL-10-GAG system via DMD was focused on the IL-10-GAG binding region predicted earlier, and made heavy usage of the optimized clustering approach named above. An important result of this endeavor is that IL-10's amino acid residue R107 significantly stands out compared to all other residues and supposedly plays a particularly important role in IL-10-GAG recognition. The collaboration with the NMR laboratory of Prof. Daniel Huster at the Universität Leipzig was fruitful: I post-processed nuclear Overhauser effect data and obtained heparin structure models, which revealed that IL-10-heparin interaction has a measurable impact on the backbone structure of the heparin molecule. These results were published in Glycobiology. In chapter 8, I propose two different scenarios about how GAG-binding to IL-10 might affect its biological function, based on the findings made in this thesis project. In conclusion, a set of methods has been developed, all of which are generically applicable for the investigation of protein-GAG systems. Regarding the IL-10-GAG system, valuable structural insights for increasing the understanding about its molecular mechanisms were derived. These observations pave the way towards unraveling GAG-mediated bioactivity of IL-10, which may then be specifically exploited, for instance in artificial ECMs for improved wound healing.

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Maingi, Vishal. "DNA nanotubes and their interaction with membranes : insights through multiscale molecular dynamics simulations". Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:65aa216b-a1a4-4d7d-a58e-b03227c4cf1d.

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DNA origami offers the possibility of developing novel membrane-spanning pores with potential applications in therapeutics and in nanosensors. In this work multiscale molecular dynamics simulation approaches have been employed to understand the dynamics of a DNA nanotube, and of its interaction with lipid bilayer membranes. All-atom simulation studies performed on the DNA nanotube model allowed exploration of its conformational dynamics, and of its interactions with ions and water molecules. Simulations under different conditions (specifically force fields and temperatures) revealed consistent properties in terms of the pore lumen shape and volume, and the gating-like motions at the mouths of the central pore. Overall the DNA nanotube model has been found to be relatively soft and porous in nature. Using the conformational information obtained from these all-atom simulations, a coarse-grained model of the DNA nanotube was developed in order to study its interactions with lipid bilayer membranes on an extended (microsecond) time scale. A number of different hydrophobic anchors which stabilize the nanotube relative to the hydrophobic core of the bilayer have been explored. Local perturbation of the membrane lipids has been observed. Energetic barriers to membrane insertion and exit for DNA nanotubes have been revealed using steered molecular dynamics approaches. A stable membrane- spanning coarse-grain DNA nanopore model was converted to all-atom resolution and used as the basis of simulation to explore the effect of high salt concentration on the stability and conformational dynamics of the pore. This confirmed that the DNA nanotube was stably embedded in the bilayer, and that ions did not form an alternative permeation pathway between the pore wall and the lipids, in contrast with other recently-reported DNA nanopore designs. Overall, these studies contribute to our understanding of the conformational dynamics and membrane interactions of DNA nanopores, thus providing guidelines to design next generation DNA nanopores rendered with controlled gating properties.

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Ohta, Hiroaki. "Molecular dynamics simulation of the plasma-surface interaction during plasma etching processes". Kyoto University, 2004. http://hdl.handle.net/2433/145252.

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Kyoto University (京都大学)
0048
新制・課程博士
博士(エネルギー科学)
甲第11119号
エネ博第97号
新制||エネ||27(附属図書館)
22669
UT51-2004-L916
京都大学大学院エネルギー科学研究科エネルギー基礎科学専攻
(主査)教授近藤克己, 教授佐野史道, 教授斧髙一
学位規則第4条第1項該当

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13

Meng, Zhiyuan. "COARSE-GRAINED SIMULATIONS OF TRANSMEMBRANE DOMAIN INTERACTIONS IN SEMAPHROIN-PLEXIN-NEUROPILIN SIGNAL SYSTEM". Case Western Reserve University School of Graduate Studies / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=case1560962527398736.

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14

Wall, Ian. "New simulation methods for the prediction of binding free energies". Thesis, University of Southampton, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.313217.

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15

Mody, Jaydeep. "Computer modelling and simulation of the interaction of keV clusters with molecular solids". Thesis, University of Surrey, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.553749.

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There is an increasing demand for techniques that are able to provide high resolution molecular imaging of biological materials. Secondary Ion Mass Spectrometry (SIMS) is one technique that has been focused on in order to achieve the above. Traditionally, SIMS has predominantly made use of atomic projectiles for this bombardment process - Atomic SIMS. However, a bit over two decades ago, a breakthrough in SIMS occurred with the advent of cluster projectiles - Cluster SIMS. This has generated deep interest for studying the nature of cluster-surface interactions. Ion-surface interactions have constantly had access to simulation programs with predictive capability. For cluster-surface interactions however, there is no such software available (yet). Some existing techniques are too slow for making predictions. Thus, the purpose of this thesis was to develop a model that was able to help in predicting SIMS relevant information for these cluster-surface interactions. The model used in the thesis is based on a simplistic energy spread approach that behaves according to a diffusional process. With the help of MD simulations, it is shown that the above approach can be a valid method for consolidating prediction capabilities for cluster-surface interactions. It has been shown that by dumping energy into the target and allowing this energy to spread, the dimension of the crater that is formed from a cluster impact can be emulated. In addition, the amount of material removed from the solid can also be matched. It was found that the following are key initial criteria that have to be met for the deposited energy. The angular distribution of the initially energetic particles is needed to be randomly and spherically distributed. The energy density (or temperature) is not required to be very sensitive although above a certain threshold. The energy requires to be deposited in such as way that its spread in the vertical direction is twice that in the lateral dimensions.

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16

Khalid, Syma. "Molecular simulation studies of the interaction between DNA and a novel macromolecular ligand". Thesis, University of Warwick, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.406780.

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17

Kang, Myungshim. "Molecular dynamics simulations and theory of intermolecular interactions in solutions". Diss., Manhattan, Kan. : Kansas State University, 2009. http://hdl.handle.net/2097/1282.

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18

Doutreligne, Sébastien. "interactive molecular dynamics software development : Application to biomolecule folding". Thesis, Sorbonne Paris Cité, 2017. http://www.theses.fr/2017USPCC180/document.

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Le repliement de biomolécules à partir de méthodes computationelles reste un grand défi. Plus particulièrement, les simulations de dynamique moléculaire tout-atomes sont intrinsèquement longues et ne permettent pas encore d’atteindre l’échelle de temps de la microseconde de façon courante. En général, un approche gros-grain est préférée pour simuler des systèmes plus grands et des échelles de temps plus longues. Les approches automatiques comme la dynamique moléculaire ne tiennent pas compte de l’expertise de l’investigateur. Ce travail de thèse explore le repliement des biomolécules au moyen de simulations de dynamique moléculaire interactives avec les modèles gros-grains OPEP et HiRE-RNA, respectivement dédiés aux acides aminés et nucléiques. Les simulations interactives sont comme les simulations classiques, mais permettent en plus à l’utilisateur d’appliquer des forces sur une sélection d’atomes et d’observer la réaction du système en direct pendant que la simulation tourne depuis un logiciel de visualisation moléculaire. Des développements logiciels dédiés ont été faits dans un de ces programmes, UnityMol, couplé aux simulations gros-grain OPEP et HiRE-RNA. Ce travail est complété par une incursion dans la biologie intégrative. L’utilisation de modèles théoriques et expérimentaux est proposée sous deux formes: l’introduction de biais dans les simulations pour les faire converger plus rapidement vers des résultats plausibles et le guidage des utilisateurs au cours de sessions interactives. Cette réflexion montre la complémentarité des méthodes théoriques et des méthodes expérimentales pour l’étude des biomolécules. Quelques essais de repliement ont été menés par des simulations interactives avec nos outils. Une approche dite collaborative (ou plus généralement “crowdsourcing”) au repliement de molécules d’ARN gros-grains avec le modèle HiRE-RNA fut menée. Le repliement de peptides a suivi dans une configuration de laboratoire avec OPEP. En complément, des aspects de réalité virtuelle et des améliorations de performance du logiciel de simulation de réseaux de ressorts BioSpring ont été explorés
The folding of biomolecules by computational methods remains a big challenge. Most notably, all-atom molecular dynamics (MD) simulations are intrinsically time consuming and do not yet commonly reach the microsecond time scale. Generally, a coarse-grained approach is preferred to simulate bigger systems and larger time scales. Automated approaches like MD do not account for the investigator expertise. The present thesis explores the folding of biomolecules with interactive molecular dynamics (IMD) simulations using the OPEP and HiRE-RNA models, respectively for amino acids and nucleic acids. IMD is like MD, but in addition, the user can apply forces on a selection of atoms and see the reaction of the system live from a molecular visualization software while the simulation is running. Dedicated software developments were done in such a program named UnityMol, coupled with coarse-grained OPEP and HiRE-RNA simulations. The picture is completed with an incursion into integrative biology. The use of theoretical and experimental models is proposed in two declinations: biasing MD simulations to faster converge to plausible results and guide users during interactive sessions. This work shows the complementarity of experimental and theoretical methods when it comes to biomolecules. A few trials at folding with IMD and our set of tools are exposed: mainly a crowdsourcing approach to RNA folding with coarse-grained HiRE-RNA models and the interactive folding of peptides in a laboratory setup of OPEP simulations. In complement, virtual reality aspects and performance enhancement of a spring network model simulation package named BioSpring have been explored

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19

Keränen, Henrik. "Advances in Ligand Binding Predictions using Molecular Dynamics Simulations". Doctoral thesis, Uppsala universitet, Beräknings- och systembiologi, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-230777.

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Biochemical processes all involve associations and dissociations of chemical entities. Understanding these is of substantial importance for many modern pharmaceutical applications. In this thesis, longstanding problems with regard to ligand binding are treated with computational methods, applied to proteins of key pharmaceutical importance. Homology modeling, docking, molecular dynamics simulations and free-energy calculations are used here for quantitative characterization of ligand binding to proteins. By combining computational tools, valuable contributions have been made for pharmaceutically relevant areas: a neglected tropical disease, an ion channel anti-drug-target, and GPCR drug-targets. We report three compounds inhibiting cruzain, the main cysteine protease of the protozoa causing Chagas’ disease. The compounds were found through an extensive virtual screening study and validated with experimental enzymatic assays. The compounds inhibit the enzyme in the μM-range and are therefore valuable in further lead optimization studies. A high-resolution crystal structure of the BRICHOS domain is reported, together with molecular dynamics simulations and hydrogen-deuterium exchange mass spectrometry studies. This work revealed a plausible mechanism for how the chaperone activity of the domain may operate. Rationalization of structure-activity relationships for a set of analogous blockers of the hERG potassium channel is given. A homology model of the ion channel was used for docking compounds and molecular dynamics simulations together with the linear interaction energy method employed for calculating the binding free-energies. The three-dimensional coordinates of two GPCRs, 5HT1B and 5HT2B, were derived from homology modeling and evaluated in the GPCR Dock 2013 assessment. Our models were in good correlation with the experimental structures and all of them placed among the top quarter of all models assessed. Finally, a computational method, based on molecular dynamics free-energy calculations, for performing alanine scanning was validated with the A2A adenosine receptor bound to either agonist or antagonist. The calculated binding free-energies were found to be in good agreement with experimental data and the method was subsequently extended to non-alanine mutations. With extensive experimental mutation data, this scheme is a valuable tool for quantitative understanding of ligand binding and can ultimately be used for structure-based drug design.

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20

Davydova, Alexandra. "MD simulation of H2 plasma/graphene interaction for innovative etching processes development". Thesis, Grenoble, 2014. http://www.theses.fr/2014GRENT054.

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Graphène est un matériau bidimensionnel unique physique, chimique et les propriétés mécaniques. Il pourrait être prometteur pour de nouvelles applications, mais le contrôle nm échelle de traitement de graphène défis la technologie actuelle, en particulier dans le traitement du plasma, empêchant ainsi le développement de la technologie à base de graphène à l'échelle industrielle
Graphene is a two-dimensional material with unique physical, chemical and mechanical properties. It could be promising for novel applications, but the nm-scale control of graphene processing challenges current technology, especially in plasma treatment, thus preventing the development of graphene based technology at industrial scale. The main issue associated with plasma/graphene processes is the atomic thickness of the material: graphene is easily damaged upon exposure to reactive plasma. One critical question to answer then: is it possible to use conventional plasma technologies to pattern/clean/dope graphene layers, as is done for other materials in the microelectronic industry?Hydrogen plasmas have been shown to be promising for graphene treatment with minimal damages, but little is known about the fundamental mechanisms involved in graphene etching. Thus, in our work, we applied classical molecular dynamics (MD) simulations of H2 plasma/graphene interaction to assist the development of three important processes. First, MD allowed us to explain the lateral etching mechanisms of graphene nanorribons (GNR) in downstream H2 plasmas, which is an important technological step to produce GNR with a width<10 nm. Second, we show that H2 plasmas can be used to clean polymeric residues from the graphene surface (selective removal of PMMA/photo-resist residues or atmospheric contaminant from its surface). Modeling results combined with experimental work shows very promising results in this application, which is demanded by the entire graphene community. Third, MD simulations were also used to assist the development of multilayer graphene processing by Atomic Layer Etching. Although irreversible damages of graphene are observed when the ion bombarding energy is in the 5-50 eV range, MD predicts a very interesting phenomenon at 20-25eV range: the implantation of hydrogen atoms and subsequent formation of H2 gas sandwiched between first two layers. This causes a pressure rise, which leads to a lift-off of the entire top graphene layer. This result from modeling suggests that H2 plasmas can be used to etch graphene layer by layer in a controlled way through an entirely new mechanism. However, in order to avoid damages of underneath layers during the processing, additional investigations should be provided.In conclusion, several novel and unexpected results were obtained during the present PhD study and MD simulations have proven to be a powerful tool to assist plasma process development. Indeed, based on this fundamental research work an ANR project was launched to develop cleaning, doping and etching processes of graphene in the ICP reactors available in the LTM laboratory, Grenoble, France. MD calculation developed during this PhD will therefore continue to be used to assist further the development of innovative processes.The current PhD project was held in LTM etching group Grenoble, France under supervision of Gilles Cunge and Emilie Despiau-Pujo in the framework of the Chair of Excellence 2010 of Prof. David Graves and financial support of Nanoscience Foundation. We would like to acknowledge collaboration with several groups from Institute Neel (Vincent Bouchiat, Laurence Magaud and Johann Coraux) and our colleagues from CEA-Grenoble, France (Okuno Hanako)

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21

Tian, Falin. "Interaction between Nanoparticles and Aggregates of Amphiphile Molecules". Thesis, Lyon, École normale supérieure, 2015. http://www.theses.fr/2015ENSL1002.

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Ayant une structure particulière avec une tête hydrophile et une queue hydrophobe, des molécules amphiphile ont de nombreuses applications importantes, comme par exemple, la fabrication des détergents, la protection et la fonctionnalisation de surfaces, etc. Des agrégats de diverses formes, micelles, véhicules, membranes etc., peuvent se former à partir des amphiphiles. La complexité de ces agrégats moléculaires rend l’étude théorique de ce type de systèmes extrêmement difficile. Jusqu’à présent, notre connaissance sur l’interaction entre des nanoparticules et des agrégats des amphiphiles reste encore incomplète. A l’aide de certaines méthodes de simulations moléculaire et une approche théorique, nous avons entrepris une série d’études pour mieux comprendre les questions fondamentales suivantes :1. Comment la présence de nanoparticules, notamment la courbure de ses surfaces, affecte l’agrégation de molécules amphiphile ?2. Comment une bicouche de lipide, une forme d’agrégat particulier des amphiphile, peut induire l’assemblage auto-organisé de nanoparticules hydrophobes ?3. Est-ce que la présence des nanoparticules peut provoquer des transitions morphologiques d’un nanotube membranaire ?
Amphiphile molecules, endowed with a particular structure containing a hydrophilic head and a hydrophobic tail, have many important applications, e.g., fabrication of detergents, surface coating or surface functionalization, etc. Molecular aggregates of various forms, micelles, vehicle, membranes, etc. can be formed from amphiphile molecules. The complexity of these molecular aggregates involving a large number of atoms make the theoretical study of these system very challenging. Up to now, our understanding of the interaction between nanoparticles and aggregates of amphiphiles remains quite incomplete. Using a variety of molecular simulation methods and some theoretical approaches (Helfrich theory and perturbation theory), we have studied the following issues in the present thesis: 1. How the presence of nanoparticles, especially due to their highly curved surfaces, affects the aggregation of the amphiphiles? 2. How a lipid bilayer, a particular amphiphile aggregate, induces the self-assembly of hydrophobic nanoparticles.3. How the morphology transition of a membrane nanotube can be induced by nanoparticles?

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22

Kognole, Abhishek A. "UNDERSTANDING CARBOHYDRATE RECOGNITION MECHANISMS IN NON-CATALYTIC PROTEINS THROUGH MOLECULAR SIMULATIONS". UKnowledge, 2018. https://uknowledge.uky.edu/cme_etds/80.

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Non-catalytic protein-carbohydrate interactions are an essential element of various biological events. This dissertation presents the work on understanding carbohydrate recognition mechanisms and their physical significance in two groups of non-catalytic proteins, also called lectins, which play key roles in major applications such as cellulosic biofuel production and drug delivery pathways. A computational approach using molecular modeling, molecular dynamic simulations and free energy calculations was used to study molecular-level protein-carbohydrate and protein-protein interactions. Various microorganisms like bacteria and fungi secret multi-modular enzymes to deconstruct cellulosic biomass into fermentable sugars. The carbohydrate binding modules (CBM) are non-catalytic domains of such enzymes that assist the catalytic domains to recognize the target substrate and keep it in proximity. Understanding the protein-carbohydrate recognition mechanisms by which CBMs selectively bind substrate is critical to development of enhanced biomass conversion technology. We focus on CBMs that target both oligomeric and non-crystalline cellulose while exhibiting various similarities and differences in binding specificity and structural properties; such CBMs are classified as Type B CBMs. We show that all six cellulose-specific Type B CBMs studied in this dissertation can recognize the cello-oligomeric ligands in bi-directional fashion, meaning there was no preference towards reducing or non-reducing end of ligand for the cleft/groove like binding sites. Out of the two sandwich and twisted forms of binding site architectures, twisted platform turned out to facilitate tighter binding also exhibiting longer binding sites. The exterior loops of such binding sites were specifically identified by modeling the CBMs with non-crystalline cellulose showing that high- and low-affinity binding site may arise based on orientation of CBM while interacting with non-crystalline substrate. These findings provide various insights that can be used for further understanding of tandem CBMs and for various CBM based biotechnological applications. The later part of this dissertation reports the identification of a physiological ligand for a mammalian glycoprotein YKL-40 that has been only known as a biomarker in various inflammatory diseases and cancers. It has been shown to bind to oligomers of chitin, but there is no known function of YKL-40, as chitin production in the human body has never been reported. Possible alternative ligands include proteoglycans, polysaccharides, and fibers such as collagen, all of which make up the mesh comprising the extracellular matrix. It is likely that YKL-40 is interacting with these alternative polysaccharides or proteins within the body, extending its function to cell biological roles such as mediating cellular receptors and cell adhesion and migration. We considered the feasibility of polysaccharides, including cello-oligosaccharides, hyaluronan, heparan sulfate, heparin, and chondroitin sulfate, and collagen-like peptides as physiological ligands for YKL-40. Our simulation results suggest that chitohexaose and hyaluronan preferentially bind to YKL-40 over collagen, and hyaluronan is likely the preferred physiological ligand, as the negatively charged hyaluronan shows enhanced affinity for YKL-40 over neutral chitohexaose. Collagen binds in two locations at the YKL-40 surface, potentially related to a role in fibrillar formation. Finally, heparin non- specifically binds at the YKL-40 surface, as predicted from structural studies. Overall, YKL-40 likely binds many natural ligands in vivo, but its concurrence with physical maladies may be related to the associated increases in hyaluronan.

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23

Panadés-Barrueta, Ramón Lorenzo. "Full quantum simulations of the interaction between atmospheric molecules and model soot particles". Thesis, Lille 1, 2020. http://www.theses.fr/2020LIL1R022.

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Nous visons à simuler avec des arguments purement quantiques (noyaux et électrons) les processus d’adsorption et de photoréactivité du NO2 adsorbé sur des particules de suie (modélisées comme de grands hydrocarbures aromatiques polycycliques, HAP) dans les conditions atmosphériques. Une description détaillée de ces processus est nécessaire pour comprendre le comportement différentiel (jour-nuit) de la production de HONO, qui est un précurseur du radical hydroxyle (OH). En particulier, le mécanisme spécifique de l’interconversion entre NO2 et HONO par la suie n’est pas encore totalement compris. En raison de sa pertinence particulière dans ce contexte, nous avons choisi le systèmePyrène-NO2.La première étape de cette étude a consisté à déterminer les configurations stables (états de transition et minima) du système Pyrène-NO2 . À cette fin, nous avons utilisé la méthode van der Waals Transition State Search using Chemical Dynamics Simulations (vdW-TSSCDS), la généralisation de l’algorithme TSSCDS récemment développée dans notre groupe. Ainsi, le présent travail représente la première application devdW-TSSCDS à un grand système (81D). Partant d’un ensemble de géométries d’entrée judicieusement choisies, la méthode susmentionnée permet de caractériser la topographie d’une surface d’énergie potentielle intermoléculaire (SEP), ou en d’autres termes, de déterminer les conformations les plus stables du système, de manière entièrement automatisée et efficace.Les informations topographiques recueillies ont été utilisées pour obtenir une description globale (fit) du potentiel d’interaction, nécessaire à l’élucidation dynamique de l’interaction intermoléculaire (physisorption), des propriétés spectroscopiques et de la réactivité des espèces adsorbées. Pour atteindre ce dernier objectif, nous avons développé deux méthodologies différentes ainsi que les progiciels correspondants. La première d’entre elles est l’algorithme SRP-MGPF (Specific Reaction Parameter Multigrid POTFIT), qui est implémenté dans le progiciel SRPTucker. Cette méthode calcule des SEPs (intermoléculaires) chimiquement précis par reparamétrage de méthodes semiempiriques, qui sont ensuite tenseur-décomposées sous forme Tucker à l’aide de MGPF.Ce logiciel a été interfacé avec succès avec la version Heidelberg du paquet MCTDH (Multi-configuration Time-Dependent Hartree). La seconde méthode permet d’obtenir la SEP directement sous la forme mathématique requise par MCTDH, d’où son nom de Sum-Of-Products Finite-Basis-Representation (SOP-FBR). La SOP-FBR constitue une approche alternative aux méthododes d’ajustement NN. L’idée la sous-tend est simple : à partir d’une expansion Tucker low rank sur la grille, nous remplaçons les fonctions de base basées sur la grille par une expansion en termes de polynômes orthogonaux. Comme dans la méthode précédente, l’intégration avec la MCTDH a été assurée.Les deux méthodes ont été testées avec succès à un certain nombre de problèmes de référence, à savoir : le Hamiltonian Hénon-Heiles, la SEP global du H2O, et la SEP d’isomérisation HONO (6D)
We aim at simulating full quantum mechanically (nuclei and electrons) the processes of adsorption and photoreactivity of NO2 adsorbed on soot particles (modeled as large Polycyclic Aromatic Hydrocarbons, PAHs) in atmospheric conditions. A detailed description of these processes is necessary to understand the differential day-nighttime behavior of the production of HONO, which is a precursor of the hydroxyl radical (OH). In particular, the specific mechanism of the soot-mediated interconversion between NO2 and HONO is to date not fully understood. Due to its particular relevance in this context, we have chosen the Pyrene-NO2 system. The first stage in this study has consisted in the determination of the stable configurations (transition states and minima) of the Pyrene-NO2 system. To this end, we have used the recently developed van der Waals Transition State Search using Chemical Dynamics Simulations (vdW-TSSCDS) method, the generalization of the TSSCDS algorithm developed in our group. In this way, the present work represents the first application of vdW-TSSCDS to a large system (81D). Starting from a set of judiciously chosen input geometries, the aforementioned method permits the characterization of the topography of an intermolecular Potential Energy Surface (PES), or in other words the determination of the most stable conformations of the system, in a fully automated and efficient manner. The gathered topographical information has been used to obtain a global description (fit) of the interaction potential, necessary for the dynamical elucidation of the intermolecular interaction (physisorption), spectroscopic properties and reactivity of the adsorbed species. To achieve this last goal, we have developed two different methodologies together with the corresponding software packages. The first one of them is the SpecificReaction Parameter Multigrid POTFIT (SRP-MGPF) algorithm, which is implemented in the SRPTucker package. This method computes chemically accurate (intermolecular) PESs through reparametrization of semiempirical methods, which are subsequently tensor decomposed into Tucker form using MGPF. This software has been successfully interfaced with the Heidelberg version of the Multi-configuration Time-DependentHartree (MCTDH) package. The second method allows for obtaining the PES directly in the mathematical form required by MCTDH, thence its name Sum-Of-Products Finite-Basis-Representation (SOP-FBR). SOP-FBR constitutes an alternative approach to NN-fitting methods. The idea behind it is simple: from the basis of a low-rank Tucker expansion on the grid, we replace the grid-based basis functions by an expansion in terms of a orthogonal polynomials. As in the previous method, an smooth integration with MCTDH has been ensured. Both methods have been successfully benchmarked with a number of reference problems, namely: the Hénon-Heiles Hamiltonian, a global H2O PES, and the HONO isomerization PES (6D)

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24

Labeye, Marie. "Molecules interacting with short and intense laser pulses : simulations of correlated ultrafast dynamics". Thesis, Sorbonne université, 2018. http://www.theses.fr/2018SORUS193/document.

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Cette thèse porte sur diﬀérents aspects des dynamiques ultra-rapides d’atomes et de molécules soumises à des impulsions laser infrarouges courtes et intenses. Nous étudions des processus fortement non linéaires tels que l’ionisation tunnel, la génération d’harmoniques d’ordre élevé ou l’ionisation au-dessus du seuil. Deux approches diﬀérentes sont utilisées. D’un côté nous mettons au point des modèles analytiques approchés qui nous permettent de construire des interprétations physiques de ces processus. D’autre part nous appuyons les interprétations données par ces modèles avec les résultats obtenus par des simulations numériques qui résolvent explicitement l’équation de Schrödinger dépendante du temps en dimension réduite. Nous étudions également une méthode numérique basée sur l’interaction de conﬁguration dépendante du temps aﬁn de pouvoir des décrire des systèmes à plusieurs électrons plus gros et plus complexes
In this thesis we study diﬀerent aspects of the ultrafast dynamics of atoms and molecules triggered by intense and short infrared laser pulses. Highly non-linear processes like tunnel ionization, high order harmonic generation and above threshold ionization are investigated. Two diﬀerent and complementary approaches are used. On the one hand we construct approximate analytical models to get physical insight on these processes. On the other hand, these models are supported by the results of accurate numerical simulations that explicitly solve the time dependent Schrödinger equation for simple benchmark models in reduced dimensions. A numerical method based on time dependent conﬁguration interaction is investigated to describe larger and more more complex systems with several electrons

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25

Cascio, Michele. "Coupled Molecular Dynamics and Finite Element Methods for the simulation of interacting particles and fields". Doctoral thesis, Università di Catania, 2019. http://hdl.handle.net/10761/4120.

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The dynamical simulation of many particle systems is currently a widespread technique in many fields: e.g. nuclear and atomic physics, computational material science, computational chemistry, molecular biology and pharmacology. Under the locution Molecular Dynamics (MD) we can regroup a variety of approaches and numerical codes, whereas the commonalities are: 1) the atomistic (or nuclear) resolution (i.e. particles are atoms or nucleons), 2) the force derivation, starting from the systems configuration, through semi-classical (also called semi-empirical) or quantum mechanics based theoretical frameworks, 3) the (generally explicit) numerical integration of the Newton-like equations of the motions to simulate the system kinetics. Within this scheme methodology variations can be found in the literature, but it is undoubtedly valid to qualify the MD meaning in the field of the scientific computation. The general scope of this Thesis work is the extension of the MD methods to the study of kinetics of larger particle (i.e. from mesoscopic dimensions and above), where effective particle-particle interactions are mediated by a field evolving self-consistently with the many particles system. This objective is mainly motivated by the applications of the method to control and predict the manipulation of mesoscopic (electrically) neutral particles by means of electromagnetic (e.m.) interactions: i.e. exploiting the so called dielectrophoresis (DEP) phenomena in the systems of electromechanical particles (EMPs). This is the specific case of study here considered, but in principle the methodology can applied after suitable adaptation to also other systems.

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26

Olubiyi, Olujide Oludayo [Verfasser]. "Investigation of the interaction between Alzheimer's abeta peptide and aggregation inhibitors using molecular simulations / Olujide Oludayo Olubiyi". Aachen : Hochschulbibliothek der Rheinisch-Westfälischen Technischen Hochschule Aachen, 2013. http://d-nb.info/1043523499/34.

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27

Olubiyi, Olujide O. [Verfasser]. "Investigation of the interaction between Alzheimer's abeta peptide and aggregation inhibitors using molecular simulations / Olujide Oludayo Olubiyi". Aachen : Hochschulbibliothek der Rheinisch-Westfälischen Technischen Hochschule Aachen, 2013. http://nbn-resolving.de/urn:nbn:de:hbz:82-opus-47016.

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28

Özdamar, Burak. "First-principles simulations of the interaction of metal-organic molecules with a surface and as building blocks for nanodevices". Thesis, Strasbourg, 2016. http://www.theses.fr/2016STRAE043/document.

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Ce travail de thèse est focalisé sur l'interaction de molécules organométalliques avec des métaux de transition. Cette thématique a un large éventail d'applications dans plusieurs domaines tels que la réalisation de nanojonctions pour la nano-électronique, la bioimagerie et le stockage d'énergie magnétique, la nano-catalyse et les applications biomédicales. Dans ce cadre général, ce projet de thèse vise la modélisation à l’échelle atomique des interactions fondamentales entre les briques moléculaires afin de comprendre leur rôle dans l’assemblage et la fonctionnalisation des nanostructures. L’outil principal utilisé est la dynamique moléculaire à partir des premiers principes selon les approches Born-Oppenheimer et Car-Parrinello. La première partie de cette thèse présente une rétrospective du domaine afin de donner une vision d’ensemble des méthodes utilisées et de l’état de l’art dans ce domaine. Le deuxième chapitre donne les éléments de base de la théorie et les méthodes qui ont été utilisées dans la thèse, au développement desquels on a aussi contribué pendant ce projet de recherche. Les résultats obtenus et leur discussion critique constituent le corps principal de cette ouvrage de thèse. Ceci est organisé dans un chapitre unique (troisième chapitre), divisé en trois sous-chapitre pour des raisons de clarté
The purpose of this study is to investigate the interaction of organometallic complexes with transition metals. This topic in question has a broad array of applications in a number of domain; realization of nanojunctions for molecular nanoelectronics, biological imaging and nanocatalysis. Within this general framework, this PhD project aims to model the fundamental interactions of molecular building blocks at the atomic level in order to understand their role in the assembly and functionalization of nanostructures. The principal tool used in this study is first-principles simulation methods such as the Born-Oppenheimer and Car-Parrinello molecular dynamics. The first chapter presents an emphasis of the current developments in the related field alongside of a retrospective on the historical developments that leads today's knowledge. The second chapter presents the basic elements of the theory behind the methods that were used in the thesis, whose development has also been contributed during this research project. Lastly, the third chapter which is organized in three sub-chapters enumerates and describes the results of the various systems studied.Molecular dynamics, constrained dynamics, molecular electronics, molecular junctions, ferrocene, fullerene, metal-organic precursors

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29

Shinto, Hiroyui. "Interfacial Microstructures and Interaction Forces between Colloidal Particles in Simple and complex Fluids-Molecular Dynamics Simulation-". Kyoto University, 1999. http://hdl.handle.net/2433/77943.

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30

Fontaine, Fabien. "Development and applications of new 3D molecular descriptors". Doctoral thesis, Universitat Pompeu Fabra, 2005. http://hdl.handle.net/10803/7080.

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Con el fin de relacionar la estructura y la actividad de series de compuestos, es importante usar descriptores moleculares relevantes. Los descriptores GRIND y VolSurf pertenecen a una nueva familia de descriptores llamado libre de alineamiento. Es decir, que no necesitan alinear los compuestos con el fin de comparar sus campos de interacciones molecular. En este estudio se ha aplicado esos descriptores para la selección de reactivos químicos a partir de una amplia base de datos. La selección se ha echo mediante un protocolo que permite maximizar la diversidad de la muestra y así obtener unos compuestos muy informativos. También se ha desarrollado nuevos descriptores de forma que están basado en los cambios de curvatura de la superficie molecular. Los resultados obtenidos indican que los nuevos descriptores de forma se integran muy bien en los descriptores GRIND originales y que permiten identificar los efectos de forma tanto favorable como desfavorable. Además, se ha desarrollado nuevos descriptores libre de alineamiento llamado 'anchor-GRIND' que usan un átomo de cada molécula como punto de referencia para la comparación de los campos de interacciones molecular. Los descriptores 'anchor-GRIND' permiten una descripción mas precisa y mas sencilla que los descriptores GRIND lo que los hace mas relevante para el análisis de ciertas familias de compuestos.
In order to correlate the differences of structure with the differences of activity of series of compounds, it is important to use relevant molecular descriptors. The GRIND and VolSurf descriptors belong to the so-called alignment-free descriptors family. In other words, they do not require to align the compounds in order to compare its molecular interaction fields. In this study, we applied these descriptors to the selection of chemical reagent from a database of compounds. The selection has been done following a protocol which allows to maximize the diversity of the sample and so to obtain some compounds highly informative. In addition we developed new shape descriptors which are based on the changes of curvature of the molecular surface. The results obtained show that the new shape descriptors are well integrated in the original GRIND descriptors. Furthermore, we designed new alignment-free descriptors called 'anchor-GRIND' which use one atom of each molecule as a reference point for the comparison of the molecular interaction fields. The 'anchor-GRIND' descriptors allow a more precise and more simple description than the GRIND descriptors, which makes them more relevant for the analysis of some families of compounds.

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31

Bodmer, Nicholas. "Molecular Investigations into the Titin-Telethonin Complex: A study in Protein-Protein Interactions". University of Cincinnati / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1439307071.

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32

Dai, Shu. "Properties of biologically relevant solution mixtures by theory and simulation". Diss., Kansas State University, 2014. http://hdl.handle.net/2097/18135.

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Doctor of Philosophy
Department of Chemistry
Paul E. Smith
Molecular Dynamics (MD) simulations have played an important role in providing detailed atomic information for the study of biological systems. The quality of an MD simulation depends on both the degree of sampling and the accuracy of force field. Kirkwood-Buff (KB) theory provides a relationship between species distributions from simulation results and thermodynamic properties from experiments. Recently, it has been used to develop new, hopefully improved, force fields and to study preferential interactions. Here we combine KB theory and MD simulations to study a variety of intermolecular interactions in solution. Firstly, we present a force field for neutral amines and carboxylic acids. The parameters were developed to reproduce the composition dependent KB integrals obtained from an analysis of the experimental data, allowing for accurate descriptions of activities involved with uncharged N-terminus and lysine residues, as well as the protonated states for the C-terminus and both aspartic and glutamic acids. Secondly, the KB force fields and KB theory are used to investigate the urea cosolvent effect on peptide aggregation behavior by molecular dynamics simulation. Neo-pentane, benzene, glycine and methanol are selected to represent different characteristics of proteins. The chemical potential derivatives with respect to the cosolvent concentrations are calculated and analyzed, and the four solutes exhibit large differences. Finally, the contributions from the vibrational partition function to the total free energy and enthalpy changes are investigated for several systems and processes including: the enthalpy of evaporation, the free energy of solvation, the activity of a solute in solution, protein folding, and the enthalpy of mixing. The vibrational frequencies of N-methylacetamide, acetone and water are calculated using density functional theory and MD simulations. We argue that the contributions from the vibrational partition function are large and in classical force fields these contributions should be implicitly included by the use of effective intermolecular interactions.

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33

Gao, Xinfeng. "Studies of the structure and interaction of several neuropeptides in membrane mimics by NMR spectroscopy and molecular dynamics simulation /". free to MU campus, to others for purchase, 2004. http://wwwlib.umi.com/cr/mo/fullcit?p3137700.

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34

Lopes, Filho Fernando César [UNESP]. "Simulações por dinâmica molecular fine-e coarse-grained das interações intermoleculares entre peptídeos antimicrobianos da família Mastoparano e membranas modelo". Universidade Estadual Paulista (UNESP), 2012. http://hdl.handle.net/11449/100887.

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Made available in DSpace on 2014-06-11T19:31:03Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-06-07Bitstream added on 2014-06-13T19:40:48Z : No. of bitstreams: 1 lopesfilho_fc_dr_sjrp_parcial.pdf: 183424 bytes, checksum: 8601f6f72a7635a3c9ada79092a5873d (MD5) Bitstreams deleted on 2015-06-25T13:01:06Z: lopesfilho_fc_dr_sjrp_parcial.pdf,. Added 1 bitstream(s) on 2015-06-25T13:03:24Z : No. of bitstreams: 1 000694954_20160706.pdf: 183130 bytes, checksum: 1526b9f9e1347a4fb71fe218102cf0ba (MD5) Bitstreams deleted on 2016-07-25T13:17:36Z: 000694954_20160706.pdf,. Added 1 bitstream(s) on 2016-07-25T13:18:45Z : No. of bitstreams: 1 000694954.pdf: 1071220 bytes, checksum: ead8820e5de7c1e29fdd2ec0459005b1 (MD5)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Peptídeos antimicrobianos são moléculas biologicamente ativas que, geralmente, tem as membranas fosfolipídicas como alvo primário. Resultados de diferentes técnicas experimentais têm sugerido que esses peptídeos permeabilizam as membranas pela formação de poros. Parte dos peptídeos caracterizados apresentam especificidade de disrupção para membranas de bactérias, em detrimento das membranas dos hospedeiros. Essa característica tem atraído a atenção da comunidade científica internacional, porque indica que estas moléculas podem ser modelos para o desenvolvimento de novos antibióticos, portanto o entendimento do mecanismo de ação, ou seja, do mecanismo de formação de poro, tem extrema importância. Simulações por Dinâmica Molecular foram produzidas para investigarmos o impacto que peptídeos antimicrobianos da família Mastoparano tem sobre membranas lipídicas modelo. Dois cenários foram explorados: (i) de baixa concentração peptídeo/lipídeo, P/L=1/128, que consistia de simulações fine-grained das interações de um peptídeo com uma bicamada pura de 128 lipídeos aniônicos (POPG) ou zwiteriônicos (POPC); (ii) de alta concentração, P/L=1/21, que abordava as interações de seis peptídeos com uma bicamada mista de 128 lipídeos POPC/POPG (1/1) usando uma modelagem coarse-grained. Tomando o peptídeo MP1 como caso paradigmático, verificamos que em baixo P/L é possível sugerir que sua característica seletiva surge da capacidade de coordenar e perturbar maior número de lipídeos em membrana aniônica comparada à neutra. Essa capacidade fica acentuada nas simulações com membrana mista, onde a atração dos lipídeos aniônicos pelos peptídeos catiônicos guiou a separação local e a formação de domínios de lipídeos aniônicos, o que facilitou o afinamento local da membrana e a formação de poro transmembrânico. Esses achados ajudam a explicar como peptídeos
Antimicrobial peptides are biologically active molecules that, usually, have the phospholipid membranes as a primary target. Results from different experimental techniques have suggested these peptides permeabilize membranes by the pore formation. Part of the characterized peptides have specificity of disruption for bacterial membranes, instead of host membrane. This feature has attracted the attention of the international scientific community, because it indicates that these molecules can be models for the development of novel antibiotics, so understanding the mechanism of action, ie, the mechanism of pore formation, is extremely important. Molecular dynamics simulations were performed to investigate the impact of antimicrobial peptides from the Mastoparano family have on model lipid membranes. Two scenarios were explored: (i) of low peptide/lipid concentration, P/L=1/128, which consisted of fine-grained simulations of the interactions of a peptide with a pure bilayer of 128 anionic (POPG) or zwitterionic (POPC) lipids; (ii) of high concentration, P/L=1/21, which addressed the interactions of six peptides with a mixed bilayer of 128 POPC/POPG (1/1) lipids, using a coarse-grained modeling. Taking the MP1 peptide as a paradigmatic case, we found that in low P/L is possible to suggest that its selective feature arises of its ability to coordinate and disturb large number of lipids in the anionic membrane compared to neutral one. This ability is accentuated in simulations with mixed membrane, where the attraction of the anionic lipids by the cationic peptides led to the local segregation and formation of POPG lipid domains, which facilitated the local thinning of the membrane and the formation of transmembrane pore. These findings help to explain how short peptides, such as MP1, are able of forming pores in a membrane whose thickness is larger than the length of the peptide

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35

Martirosyan, Vahagn. "Atomistic simulations of H2 and He plasmas modification of thin-films materials for advanced etch processes". Thesis, Université Grenoble Alpes (ComUE), 2017. http://www.theses.fr/2017GREAT101/document.

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Ce travail de thèse aborde l’un des défis technologiques liés au développement de nouvelles générations de transistors (FinFET, FDSOI), pour lesquels la gravure de couches ultraminces révèle plusieurs problèmes. En particulier, la gravure des espaceurs nitrure (SiN) doit être réalisée avec une précision nanométrique sans endommager les couches sous-jacentes, étape qui ne peut plus être réalisée par des plasmas conventionnels continus. Afin de dépasser cette limitation, une approche innovante a été récemment développée (dite Smart-Etch), qui s’appuie sur l'implantation d’ions légers et se déroule en deux étapes. Premièrement, le matériau à graver est exposé à un plasma ICP ou CCP d’hydrogène (H2) ou d’hélium (He); dans une deuxième étape, la couche modifiée est retirée sélectivement par gravure humide ou exposition à des réactifs gazeux. Afin d’appréhender les mécanismes fondamentaux de la première étape et assister le développement de cette nouvelle technologie, des simulations de dynamique moléculaire (MD) ont été réalisées pour étudier l'interaction des plasmas H2/He avec des couches de Si/SiN. La MD a été utilisée pour examiner comment la modification de ces substrats est affectée par l’énergie ionique, la dose ionique, la composition ionique ou le rapport flux de radicaux/ flux d’ions (dans le cas d’un plasma H2). En accord avec les expériences, les simulations de bombardement ionique He+ ou Hx+ (x = 1-3) sur Si/SiN montrent que l’implantation ionique est auto-limitée, et que l’évolution de la surface se déroule en deux étapes : une rapide modification en volume (sans gravure) suivie d'une saturation lente et de la formation d'une couche implantée stable en régime permanent (état stationnaire). Les mécanismes d'endommagement induit par les ions (rupture des liaisons Si-Si ou Si-N, piégeage/désorption d’He ou H2, formation de groupes SiHx (x = 1-3) en profondeur), sont étudiés et permettent d’apporter de nouveaux éléments de compréhension aux technologies Smart-Cut et Smart-Etch. L’exposition de substrats Si/SiN à un plasma H2 (impacts d’ions Hx+ et de radicaux H) a également été étudiée pour différentes conditions plasma. Dans ce cas, une transformation auto-limitée est observée mais les couches modifiées/hydrogénées sont simultanément gravées pendant l'implantation ionique, à un taux 10 fois inférieur pour SiN par rapport à Si. Les simulations montrent que modifier des substrats Si/SiN avec une précision nanométrique nécessite un contrôle prudent de l’énergie et du flux des ions incidents. En particulier, les faibles doses ioniques doivent être évitées car l’évolution de la surface ne peut pas être contrôlée précisément en régime transitoire (modification rapide). Dans les plasmas H2, les énergies ioniques élevées induisent des couches modifiées plus épaisses mais des taux d'hydrogénation plus faibles et moins homogènes. La composition ionique et le rapport flux de radicaux/ flux ions (Γ) doivent également être controllés avec précaution, notamment car la vitesse de gravure du matériau augmente avec Γ, ce qui empêche entre-autre la possibilité du Smart-Etch pour le silicium. Les simulations MD réalisées dans cette thèse permettent de clarifier divers phénomènes inexpliqués observés dans le Smart-Etch expérimentalement, et de révéler quelques problèmes possibles dans ce nouveau procédé. Finalement, une gamme de paramètres plasma est proposée pour optimiser cette première étape de Smart-Etch et contrôler la modification de SiN avec une précision sous-nanométrique
This PhD thesis focuses on technological challenges related to the development of advanced transistors (FinFET, FDSOI), where the etching of thin films reveals several issues. In particular, the etching of silicon nitride spacers should be achieved with a nanoscale precision without damaging the underlayers, a step which cannot be addressed by conventional CW plasmas. To overpass this limitation, an innovative approach was recently developed (so-called Smart Etch), which is based on light ion implantation and composed of two steps. First, the material to be etched is modified by exposure to a hydrogen (H2) or helium (He) ICP or CCP plasma; in a second step, the modified layer is selectively removed using wet etching or gaseous reactants only. To support the fundamental understanding of the first step and assist the development of this new technology, molecular dynamics (MD) simulations were performed to study the interaction between silicon/silicon nitride films and hydrogen/helium plasmas. MD was used to investigate how the substrates modification is affected by the ion energy, the ion dose, the ion composition or the radical-to-ion flux ratio (in the case of a H2 plasma). In agreement with experiments, simulations of He+ or Hx+ (x=1-3) ion bombardment of Si/SiN show that a self-limited ion implantation takes place with a surface evolution composed of two stages: a rapid volume modification (with no etching) followed by a slow saturation and the formation of a stable He- or H- implanted layer at steady state. The mechanisms of ion-induced damage (Si-Si or Si-N bond breaking, He or H2 trapping/desorption, SiHx (x=1-3) complex creation) are investigated and allow to bring new insights to both the Smart Cut and Smart Etch technologies. Si/SiN exposure to various H2 plasma conditions (with both Hx+ ions and H radicals) was then studied. In this case, a self-limited transformation is observed but the H-modified layers are simultaneously etched during the ion implantation, at a rate ~10 times smaller for SiN compared to Si. Simulations show that to modify Si/SiN thin films with a nanoscale precision by H2 or He plasmas, both the ion energy and the ion flux have to be controlled very cautiously. In particular, low ion doses, where the substrate evolution is in rapid modification stage, must be avoided since the substrate evolution cannot be precisely controlled. In H2 plasmas, high ion energies induce thicker modified layers but smaller and less homogeneous hydrogenation rates. The ion composition and the radical-to-ion flux ratio Γ must be considered as well, since the etch rate increases with Γ, compromising even the possibility to achieve a Smart Etch of silicon. The MD simulations performed in this thesis enable to clarify various unexplained phenomena seen in the Smart-Etch experimentally, and reveal some possible issues in this new process. In the end, a range for plasma parameters is proposed to optimize this first step of the Smart Etch process and to control the modification of SiN with a sub-nanoscale precision

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36

Madeleine, Noelly. "Recherche d'inhibiteurs de l'interaction Lutheran-Laminine par des techniques de modélisation et de simulation moléculaires". Thesis, La Réunion, 2017. http://www.theses.fr/2017LARE0054/document.

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La drépanocytose est une maladie génétique qui se caractérise par des globules rouges en forme de faucille. Chez les personnes atteintes de drépanocytose, ces globules rouges (GR) adhèrent à l’endothélium vasculaire et provoquent ainsi une vaso-occlusion. Ce phénomène s’explique par la surexpression de la protéine Lutheran (Lu) à la surface des globules rouges falciformes qui se lie fortement à la Laminine (Ln) 511/521 exprimée par l’endothélium vasculaire enflammé. Le but de cette étude est d’identifier un inhibiteur d’interaction protéine-protéine (PPI) qui possède une forte probabilité de liaison à Lu afin d’inhiber l’interaction Lu-Ln 511/521. Un criblage virtuel de 1 295 678 composés ciblant la protéine Lu a été réalisé. La validation préalable d’un protocole de scoring a été envisagée sur la protéine CD80 qui présente un site de liaison avec des caractéristiquestopologiques et physico-chimiques similaires au site de liaison prédit sur Lu ainsi que plusieurs ligands avec des constantes d’affinité connues. Ce protocole contient différentes étapes de sélection basées sur les affinités calculées (scores), des simulations de dynamique moléculaire et les propriétés moléculaires. Un protocole de scoring fiable a été validé sur CD80 avec le programme de docking DOCK6 et les fonctions de scoring XSCORE et MM-PBSA ainsi qu’avec la méthode decalcul FMO. L’application de ce protocole sur Lu a permis d’obtenir deux ligands validés par des tests in vitro qui font l’objet d’un dépôt de brevet. La fonction de scoring XSCORE a permis d’identifier neuf autres ligands qui semblent aussi être des candidats prometteurs pour inhiber l’interaction Lu-Ln 511/521
Drepanocytosis is a genetic blood disorder characterized by red blood cells that assume an abnormal sickle shape. In the pathogenesis of vaso-occlusive crises of sickle cell disease, red blood cells bind to the vascular endothelium and promote vaso-occlusion. At the surface of these sickle red blood cells, the overexpressed protein Lutheran (Lu) strongly interacts with the Laminin (Ln) 511/521.The aim of this study was to identify a protein-protein interaction (PPI) inhibitor with a highprobability of binding to Lu for the inhibition of the Lu-Ln 511/521 interaction. A virtual screening was performed with 1 295 678 compounds that target Lu. Prior validation of a robust scoring protocol was considered on the protein CD80 because this protein has a binding site with similar topological and physico-chemical characteristics and it also has a series of ligands with known affinity constants. This protocol consisted of multiple filtering steps based on calculated affinities (scores), molecular dynamics simulations and molecular properties. A robust scoring protocol was validated on the protein CD80 with the docking program DOCK6 and the scoring functions XSCORE and MM-PBSA and also with the FMO method. This protocol was applied to the protein Lu and we found two compounds that were validated by in vitro studies. The protection of these ligands by a patent is under process. Nine other compounds were identified by the scoring functionXSCORE and seem to be promising candidates for inhibiting the Lu-Ln 511/521 interaction

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37

Miller, Mark Stephen. "Use of osmotic coefficient measurements to validate and to correct the interaction thermodynamics of amino acids in molecular dynamics simulations". Diss., University of Iowa, 2018. https://ir.uiowa.edu/etd/6476.

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Molecular dynamics simulations are an increasingly valuable tool to biochemical researchers: advances in computational power have expanded the range of biomolecules that can be simulated, and parameters describing these interactions are increasingly accurate. Despite substantial progress in force field parameterization, recent simulations of protein molecules using state-of-the-art, fixed-charge force fields revealed that the interactions among and within protein molecules can be too favorable, resulting in unrealistic aggregation or structural collapse of the proteins being simulated. To understand why these protein-protein interactions are so over-stabilized, I first assessed the ability of simulation force fields to represent accurately the interactions of individual amino acids, employing an osmotic pressure simulation apparatus that enabled direct comparison with experiment. Surprisingly, simulations of most of the amino acids resulted in behavior that was in strong agreement with experiment. A number of amino acids, however—notably those that contain hydroxyl groups and those that carry a formal charge—interacted in ways that were clearly inaccurate. Additionally, some commonly-used force fields failed to accurately represent the interactions of amino acids in a consistent manner. By further investigating the interactions of the functional groups of these amino acids, I was able not only to determine some of the root causes of individual amino acid inaccuracies, but also to implement simple modifications that brought the interactions of these small molecules and amino acids in stronger accord with experiment. These studies have highlighted some of the shortcomings in popular simulation force fields, and have proposed useful modifications to address them. Still, there is additional work that must be—and is being—conducted in order to correctly model the interaction behavior of proteins in simulation.

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38

Sánchez, René Javier. "Dissecting contributions of structural elements of PSGL-1 to its interaction with P-selectin using AFM". Thesis, Georgia Institute of Technology, 2003. http://hdl.handle.net/1853/17961.

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39

Bärenwald, Ruth [Verfasser]. "Solid-state NMR investigations and MD simulations of lipid bilayers in interaction with amphiphilic and polyphilic molecules / Ruth Bärenwald". Halle, 2018. http://d-nb.info/1177034123/34.

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40

Singh, Vidisha. "Integrative analysis and modeling of molecular pathways dysregulated in rheumatoid arthritis Computational systems biology approach for the study of rheumatoid arthritis: from a molecular map to a dynamical model RA-map: building a state-of-the-art interactive knowledge base for rheumatoid arthritis Automated inference of Boolean models from molecular interaction maps using CaSQ". Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASL039.

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La polyarthrite rhumatoïde (PR) est unemaladie auto-immune complexe qui entraîne uneinflammation synoviale et une hyperplasie pouvantprovoquer une érosion osseuse et une destruction ducartilage dans les articulations. L'étiologie de la PR restepartiellement inconnue, mais elle implique de multiplescascades de signalisation croisées et l'expression demédiateurs pro-inflammatoires. Dans la première partie demon projet de doctorat, nous présentons un effortsystématique pour construire une base de connaissancessur la PR, entièrement annotée et validée par des experts.Cette carte de la PR illustre les voies moléculaires et designalisation importantes impliquées dans la maladie. Latransduction du signal est systématiquement représentéedes récepteurs au noyau en utilisant la représentationstandard de notation graphique en biologie des systèmes(SBGN). La curation manuelle est basée sur des critèresstricts et spécifique aux études sur l'homme, limitantl'apparition de faux positifs sur la carte. Cette carte peutservir de base de connaissances interactive pour la maladiemais aussi de tableau pour la visualisation des donnéesomiques. De plus, c’est une excellente base pour ledéveloppement d'un modèle informatique. La naturestatique de la carte PR pourrait fournir une compréhensionrelativement limitée du comportement émergeant dusystème dans différentes conditions. La modélisationinformatique pourra révéler les propriétés dynamiques duréseau par le biais de perturbations in silico et peut êtreutilisée pour tester et prédire des hypothèses.Dans la deuxième partie du projet, nous présentons unpipeline permettant la construction automatisée d'un grandmodèle booléen, à partir d'une carte d'interactionsmoléculaires. Pour cela, nous avons développé l'outilCaSQ (CellDesigner as SBML-qual), qui automatise laconversion des cartes moléculaires en modèles booléensexécutables basés sur la topologie et la sémantique descartes. Le modèle booléen résultant pourrait être utilisépour des simulations in silico afin de reproduire lecomportement biologique connu du système et de prédirede nouvelles cibles thérapeutiques. Pour l'analyse deperformance de l’outil, nous avons utilisé différentescartes et modèles de maladies en mettant l'accent sur lagrande carte moléculaire de la PR.Dans la troisième partie du projet, nous présentons nosefforts pour créer un modèle dynamique (booléen) àgrande échelle pour les synoviocytes de type fibroblastede polyarthrite rhumatoïde (RA-FLS). Parmi denombreuses cellules de l'articulation et du systèmeimmunitaire impliquées dans la pathogenèse de la PR, lesRA-FLS joue un rôle important dans l'initiation et laperpétuation de l'inflammation articulaire destructrice.Les RA-FLS expriment des cytokinesimmunomodulatrices, des molécules d'adhésion et desenzymes de modélisation matricielle. De plus, les RAFLSprésentent des taux de prolifération élevés et unphénotype résistant à l'apoptose. Les RA-FLS peuventégalement se comporter comme les principaux moteurs del'inflammation, et les thérapies dirigées contre les RA FLSpourraient devenir une approche complémentaire auximmunothérapies. Le défi est de prédire les conditionsoptimales qui favoriseraient l'apoptose des RA FLS,limiteraient l'inflammation, ralentiraient le taux deprolifération et minimiseraient l'érosion osseuse et ladestruction du cartilage
Rheumatoid arthritis (RA) is a complexautoimmune disease that results in synovial inflammationand hyperplasia leading to bone erosion and cartilagedestruction in the joints. The aetiology of RA remainspartially unknown, yet, it involves a variety of intertwinedsignalling cascades and the expression of pro-inflammatorymediators. In the first part of my PhD project, we present asystematic effort to construct a fully annotated, expertvalidated, state of the art knowledge-base for RA. The RAmap illustrates significant molecular and signallingpathways implicated in the disease. Signal transduction isdepicted from receptors to the nucleus systematically usingthe systems biology graphical notation (SBGN) standardrepresentation. Manual curation based on strict criteria andrestricted to only human-specific studies limits theoccurrence of false positives in the map. The RA map canserve as an interactive knowledge base for the disease butalso as a template for omic data visualization and as anexcellent base for the development of a computationalmodel. The static nature of the RA map could provide arelatively limited understanding of the emerging behaviorof the system under different conditions. Computationalmodeling can reveal dynamic network properties throughin silico perturbations and can be used to test and predictassumptions.In the second part of the project, we present a pipelineallowing the automated construction of a large Booleanmodel, starting from a molecular interaction map. For thispurpose, we developed the tool CaSQ (CellDesigner asSBML-qual), which automates the conversion ofmolecular maps to executable Boolean models based ontopology and map semantics. The resulting Booleanmodel could be used for in silico simulations to reproduceknown biological behavior of the system and to furtherpredict novel therapeutic targets. For benchmarking, weused different disease maps and models with a focus onthe large molecular map for RA.In the third part of the project we present our efforts tocreate a large scale dynamical (Boolean) model forrheumatoid arthritis fibroblast-like synoviocytes (RAFLS).Among many cells of the joint and of the immunesystem involved in the pathogenesis of RA, RA FLS playa significant role in the initiation and perpetuation ofdestructive joint inflammation. RA-FLS are shown toexpress immuno-modulating cytokines, adhesionmolecules, and matrix-modelling enzymes. Moreover,RA-FLS display high proliferative rates and an apoptosisresistantphenotype. RA-FLS can also behave as primarydrivers of inflammation, and RA FLS-directed therapiescould become a complementary approach to immunedirectedtherapies. The challenge is to predict the optimalconditions that would favour RA FLS apoptosis, limitinflammation, slow down the proliferation rate andminimize bone erosion and cartilage destruction

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41

Gehrcke, Jan-Philip [Verfasser], M. Teresa [Akademischer Betreuer] Pisabarro, Stefan [Akademischer Betreuer] Diez y Daniel [Akademischer Betreuer] Huster. "Investigation of the interleukin-10-GAG interaction using molecular simulation methods / Jan-Philip Gehrcke. Gutachter: Stefan Diez ; Daniel Huster. Betreuer: M. Teresa Pisabarro". Dresden : Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2015. http://d-nb.info/1069518204/34.

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42

Zhang, Wei. "Computational Methods in Biomolecules:Study of Hydrophilic Interactions in Protein Folding & Constant-pH Molecular Simulation of pH Sensitive Lipid MORC16". Scholarly Commons, 2018. https://scholarlycommons.pacific.edu/uop_etds/3145.

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Water molecules play a significant role in biological process and are directly involved with bio-molecules and organic compounds and ions. Recent research has focused on the thermal dynamics and kinetics of water molecules in solution, including experimental (infrared spectroscopy and Raman spectroscopy) and computational (Quantum Mechanics and Molecular Dynamics) approaches. The reason that water molecules are so unique, why they have such a profound influence on bio-activity, why water molecules show some anomalies compared to other small molecules, and where and how water molecules exert their influence on solutes are some of the areas under study. We studied some properties of hydrogen bond networks, and the relationship of these properties with solutes in water. Molecular dynamics simulation, followed by an analysis of “water bridges”, which represent protein-water interaction have been carried out on folded and unfolded proteins. Results suggest that the formation of transient water bridges within a certain distance helps to consolidate the protein, possibly in transition states, and may help further guide the correct folding of proteins from these transition states. This is supporting evidence that a hydrophilic interaction is the driving force of protein folding. Biological membranes are complex structures formed mostly by lipids and proteins. For this reason the lipid bilayer has received much attention, through computation and experimental studies in recent years. In this dissertation, we report results of a newly designed pH sensitive lipid MORC16, through all-atom and coarse-grained models. The results did not yield a MORC16 amphiphile which flips its conformation in response to protonation. This may be due to imperfect force field parameters for this lipid, an imperfect protonation definition, or formation of hydrogen bond does not responsible for conformation flip in our models. Despite this, some insights for future work were obtained.

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Shahsavari, Bedoustani Ashkan. "Dynamique des polymères à grande densité d'interactions fortes". Thesis, Lyon, 2017. http://www.theses.fr/2017LYSE1133/document.

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L'objectif de la thèse a été d'étudier les propriétés dynamiques des polymères à grande densité d'interactions fortes intermoléculaires, en fonction de l'énergie et de la densité de ces interactions. Cette étude s'est effectuée par la méthode de la dynamique moléculaire. Deux types d'interactions fortes ont étés proposés et implémentés numériquement. Un premier modèle dit isotrope dans lequel des interactions fortes sont modélisées par un potentiel isotrope, représentant par exemple des interactions ioniques. Et un second modèle dans lequel nous avons choisi un potentiel directionnel, modélisant les liaisons polaires ou les liaisons hydrogènes. L'unité de l'énergie des interactions fortes intermoléculaires a été fixée par rapport aux forces de Van der Waals des monomères non polaires qui forment la partie principale des polymères considérés J'ai étudié la dynamique de la relaxation à grande échelle (mode de Rouse) en fonction des paramètres pertinents (l'énergie et la densité) dans le régime dit Williams-Landel-Ferry (WLF). Ensuite, nous avons étudié les mécanismes de relaxation à petite échelle (monomérique) en cherchant à mettre en évidence des mécanismes spécifiques à ces polymères à fortes interactions. Nous avons également étudié la relaxation du stress. Nous avons mis en évidence une relaxation à temps intermédiaire entre le temps monomérique te les temps longs pendant laquelle le stress reste à un niveau relativement élevé, sur des échelles de temps comparables à ceux des mécanismes de relaxation spécifiques mis en évidence au niveau microscopique. Ce régime spécifique de relaxation du stress qui n'est pas observé à faible fraction de liaisons fortes est susceptible de dominer les propriétés mécaniques et viscoélastiques de ces polymères à l'état fondu. Nous avons également considéré le comportement ultime de ces polymères en étudiant les mécanismes de la cavitation. L'énergie à la rupture peut être augmentée par la présence de liaisons fortes à suffisamment forte densité le long des chaînes. Les systèmes à forte densité de liaisons polaires ne font plus apparaître de cavitation mais exhibent un comportement de strain hardening
The aim of the thesis is to study the dynamic properties of polymers with high densities of strong intermolecular interactions, depending on the energy and the density of these interactions. This study is carried out by the molecular dynamics method

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44

Morelon, Nhan Duc. "Dynamique moléculaire du composé d'inclusion TANO-heptane : une étude combinée : simulation numérique/diffusion quasiélastique incohérente des neutrons". Université Joseph Fourier (Grenoble), 1999. http://www.theses.fr/1999GRE10015.

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Les composes d'inclusion du tano sont des complexes moleculaires constitues de deux especes chimiques. Les molecules de tano forment une matrice ayant une structure en canaux, dans laquelle sont incluses une grande variete de molecules lineaires (alcanes, polymeres, etc). La complexite et la variete du desordre dynamique rencontre dans ces cristaux plastiques nous a amener a completer les etudes experimentales anterieures par des simulations de dynamique moleculaire. Apres un resume des principales caracteristiques des composes d'inclusion du tano (descriptions des phases basse et haute temperature du tano-heptane, transitions de phase) et un rappel detaille des resultats obtenus precedemment par diffusion quasielastique des neutrons par bee etal, les methodes de simulation utilisees par la suite sont exposees de maniere synthetique. Nous introduisons aussi dans cette partie les fonctions utilisees en diffusion neutronique et leurs liens avec les resultats issus des simulations. Nous decrivons ensuite en detail les procedures utilisees pour mettre au point le potentiel d'interaction empirique a partir des donnees experimentales disponibles et des resultats de calculs ab initio. Cette phase, dite de parametrisation, determine de facon cruciale la qualite des simulations de dynamique moleculaire. Un premier test du potentiel empirique est realise en comparant les structures moleculaires calculees aux resultats experimentaux et ab initio. La description et l'analyse approfondie des simulations de dynamique moleculaire de la phase haute temperature du tano-heptane est ensuite detaillee. Les trajectoires atomiques simulees nous ont permis de calculer les spectres de diffusion quasielastique incoherente et ainsi d'effectuer une comparaison directe de nos simulations aux etudes experimentales. Des etudes experimentales de diffusion quasielastique sous pression concluent notre travail et montrent finalement que les composes d'inclusion du tano sont encore loin d'etre parfaitement compris.

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45

Dupin, Lucie. "Validation et criblage de nouvelles molécules anti-infectieuses sur microarray : applications à Pseudomonas aeruginosa". Thesis, Lyon, 2016. http://www.theses.fr/2016LYSEC018/document.

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Pseudomonas aeruginosa (PA) est la troisième bactérie impliquée dans les maladies nosocomiales et est la principale cause de mortalité des patients atteints de la mucoviscidose. PA est résistante à la plupart des traitements antibiotiques. Trouver de nouvelles stratégies thérapeutiques est devenu un enjeu majeur de santé publique, l’une d’entre elles est l’inhibition de facteurs de virulence. Parmi ceux-ci, les lectines sont des protéines impliquées dans l’adhésion et la formation de biofilm via des interactions avec des sucres (PA-IL, PA- IIL, FliC, FliD, PilA, PilY1 et CupB6).Le but de ce travail est donc de trouver des leurres moléculaires ayant une forte affinité pour ces lectines. Ceux-ci sont des motifs saccharidiques présentés de façon multivalente : glycoclusters. De part leur grande diversité structurale et leur faible quantité, un outil de criblage innovant a été développé qui consiste en une lame de verre microstructurée : le glycocluster-microarray. Les glycoclusters sont immobilisés de manière ordonnée par DNA Directed Immobilization (DDI). Deux méthodes de criblage ont été développées grâce à cet outils : 1) le criblage en solution et par compétition d’une bibliothèque de motifs saccharidiques et 2) le criblage d’une bibliothèque de glycoclusters immobilisés sur le microarray. Avec cet outil, des protocoles de mesures d’IC50 et de Kd ont aussi été fiabilisés pour caractériser les meilleurs candidats inhibiteurs des lectines. Le glycocluster- microarray présente l’avantage de n’utiliser qu’une très faible quantité de matériel (quelques picomoles) et permet de réaliser diverses analyses en parallèle.Afin de valider cet outil, une étude sur l’impact de la densité de surface en glycocluster a été menée. Le criblage de plus de 150 motifs saccharidiques a permis de sélectionner ceux ayant une forte affinité pour les lectines. L’analyse sur microarray complétée par de la modélisation moléculaire d’une bibliothèque de glycoclusters, possédant ces motifs et différentes topologies, valences et propriétés (aromaticité, charge,…), a permis d’identifier les paramètres clés dirigeant les relations structure-affinité. Une activité anti-biofilm chez PA a été démontrée avec les meilleurs glycoclusters ciblant PA-IL.Tester l’activité in vivo, chez l’animal, des meilleurs candidats est une voie à explorer. Cibler d’autres lectines comme celles présentes sur le flagelle et les pili de PA et notamment impliquées dans son adhésion précoce est aussi une voie à développer. Pour cela, des tests préliminaires ont été présentés et d’autres sont en cours faisant appel à l’utilisation de bactéries entières ainsi qu’à une détection sans marquage des lectines
Summary: Pseudomonas aeruginosa (PA) is the third pathogen involved in nosocomial diseases and the major cause of mortality of cystic fibrosis patients. PA develops resistance to antibiotics treatments. And so, developing new therapeutic strategies is a public health issue. One of the promising strategies is to inhibit virulence factors involved in the adhesion and the biofilm formation of PA. Some of these virulence factors are lectins which interact with sugars (PA-IL, PA-IIL, FliC, FliD, PilA, PilY1 and CupB6).The goal of this work is to find molecular decoys which have a strong affinity for these lectins. These are saccharidic units with a multivalent display: glycoclusters. An innovative screening tool has been developed: the glycocluster-microarray, to study lectin/glycocluster interactions. It is a microstructured glass slide where glycoclusters are immobilized by DNA Directed Immobilization (DDI). Two screening methods have been developed with this microarray: 1) the screening in solution and by competition of a saccharidic units library and2) the screening of a glycoclusters library immobilized on the microarray. Protocols of IC50 and Kd measurements have also been developed with this tool to characterize the best lectins inhibitors. This tool allows to use few amount of material (few picomoles) and to do parallel analysis.To validate the microarray, a study of the impact of glycoclusters surface density has been done. The screening of more than 150 saccharidic units allowed the selection of the ones that display the best affinity forlectins. The analysis, on microarray and molecular simulations, of the glycoclusters library displaying thesesaccharidic units and several topologies, valences and properties (aromaticity, charge,…) enable to identify key parameters of structure-affinity relationships. An anti-biofilm activity has been observed for the best glycoclusters targeting PA-IL.Testing in vivo activity of these best candidates will be explored. Targeting others lectins such as the ones on the flagella and pili of PA and involved in the early adhesion needs also to be developed. To this end, preliminary tests have been showed and some are in progress

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46

Simard, Jean. "Collaboration haptique étroitement couplée pour la manipulation moléculaire interactive". Phd thesis, Université Paris Sud - Paris XI, 2012. http://tel.archives-ouvertes.fr/tel-00688036.

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Le docking moléculaire est une tâche complexe, difficile à appréhender pour une personne seule. C'est pourquoi, nous nous proposons d'étudier la distribution cognitive des charges de travail à travers la collaboration. Une plate-forme distribuée de déformation moléculaire interactive a été mise en place afin d'étudier les avantages mais aussi les limites et les contraintes du travail collaboratif étroitement couplé. Cette première étude, basée sur trois expérimentations, a permis de valider l'intérêt d'une approche collaborative pour des tâches complexes à fort couplage. Cependant, elle a mis en évidence des conflits de coordination ainsi que des problématiques liées à la dynamique d'un groupe. Suite à cette première étude, nous avons proposés une nouvelle configuration de travail associée à des métaphores de communication haptiques afin d'améliorer la communication et les interactions entre les différents collaborateurs. Une dernière expérimentation avec des biologistes a permis de montrer l'utilité de la communication haptique pour le travail collaboratif sur des tâches complexes à fort couplage.

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47

Fabre, Gabin. "Molecular interaction of natural compounds with lipid bilayer membranes : Towards a better understanding of their biological and pharmaceutical actions". Thesis, Limoges, 2015. http://www.theses.fr/2015LIMO0122/document.

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Une des clés pour comprendre les mécanismes d’action biologiques des molécules naturelles et thérapeutiques est leur faculté à incorporer ou traverser les membranes lipidiques. Parce que les méthodes expérimentales sont parfois couteuses et répondent partiellement aux questions posés par les interactions composé-membrane, la modélisation moléculaire est devenue une sérieuse alternative. Les simulations de dynamique moléculaire ont ouvert de nombreuses perspectives ces dernières années en offrant la possibilité de décrire ces interactions intermoléculaires au niveau atomique. À l’aide de ces simulations, nous avons évalué la capacité de plusieurs composés (polyphénols, vitamines E et C, plantazolicine et carprofènes) à s’incorporer dans les membranes. Ces molécules ont été choisies pour leurs activités biologiques diverses, à savoir (i) activité antioxydante, précisément inhibition de la peroxydation lipidique, (ii) activité antibiotique et possibilité de former un pore transmembranaire, et (iii) inhibition d’enzymes impliquées dans la maladie d’Alzheimer. Leurs positions et orientations ainsi que leur capacité à s’accumuler ou à traverser les membranes ont été évaluées pour comprendre leurs mécanismes d’action.Dans le but d’utiliser les simulations de dynamique moléculaire en drug design, l’accent a été mis sur la précision des calculs, qui dépend de la qualité sous-jacente du modèle utilisé. En corrélant données expérimentales et théoriques, la méthodologie de nos modèles a été systématiquement revisitée. Le choix du champ de force, les paramètres des composés étudiés ainsi que la composition de la membrane sont en particulier apparus comme d’importants facteurs dans la description des interactions entre les molécules naturelles et thérapeutiques et les membranes. Des mélanges de lipides contenant du cholestérol ont notamment été utilisés et ont montré un impact significatif sur les résultats obtenus
One of the key lockers to understand mechanisms of biological action of drugs and natural compounds is their capacity to incorporate/cross lipid bilayer membranes. In the light of demanding experimental techniques, in silico molecular modelling has become a powerful alternative to tackle these issues. In the past few years, molecular dynamics (MD) has opened many perspectives, providing an atomistic description of the related intermolecular interactions. Using MD simulations, we have explored the capacity of several compounds (polyphenols, vitamins E and C, plantazolicin, carprofens) to incorporate lipid bilayer membranes. The different compounds were chosen according to their different biological functions, namely (i) antioxidant activity against lipid peroxidation, (ii) antimicrobial activity with the possibility of trans-membrane pore formation, and (iii) inhibition of enzymes involved in Alzheimer’s disease. In order to rationalize their mechanisms of action, their position and orientation in membranes as well as their capacity to accumulate or permeate lipid bilayers were assessed. Having in mind a predictive purpose in drug design for MD simulations, the accuracy of the results relies on the quality of the in silico membrane models. By ensuring relationships between experimental and theoretical data, methodological improvements have been proposed. In particular, force field selection, xenobiotic parameterization and bilayer constitution emerged as crucial factors to appropriately depict drug-membrane interactions. For the latter issue, lipid mixtures e.g., including cholesterol have been developed

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48

Andér, Martin. "Computational Analysis of Molecular Recognition Involving the Ribosome and a Voltage Gated K+ Channel". Doctoral thesis, Uppsala universitet, Institutionen för cell- och molekylärbiologi, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-101413.

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Over the last few decades, computer simulation techniques have been established as an essential tool for understanding biochemical processes. This thesis deals mainly with the application of free energy calculations to ribosomal complexes and a cardiac ion channel. The linear interaction energy (LIE) method is used to explore the energetic properties of the essential process of codon–anticodon recognition on the ribosome. The calculations show the structural and energetic consequences and effects of first, second, and third position mismatches in the ribosomal decoding center. Recognition of stop codons by ribosomal termination complexes is fundamentally different from sense codon recognition. Free energy perturbation simulations are used to study the detailed energetics of stop codon recognition by the bacterial ribosomal release factors RF1 and RF2. The calculations explain the vastly different responses to third codon position A to G substitutions by RF1 and RF2. Also, previously unknown highly specific water interactions are identified. The GGQ loop of ribosomal RFs is essential for its hydrolytic activity and contains a universally methylated glutamine residue. The structural effect of this methylation is investigated. The results strongly suggest that the methylation has no effect on the intrinsic conformation of the GGQ loop, and, thus, that its sole purpose is to enhance interactions in the ribosomal termination complex. A first microscopic, atomic level, analysis of blocker binding to the pharmaceutically interesting potassium ion channel Kv1.5 is presented. A previously unknown uniform binding mode is identified, and experimental binding data is accurately reproduced. Furthermore, problems associated with pharmacophore models based on minimized gas phase ligand conformations are highlighted. Generalized Born and Poisson–Boltzmann continuum models are incorporated into the LIE method to enable implicit treatment of solvent, in an effort to improve speed and convergence. The methods are evaluated and validated using a set of plasmepsin II inhibitors.

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49

Carlsson, Jens. "Challenges in Computational Biochemistry: Solvation and Ligand Binding". Doctoral thesis, Uppsala University, Department of Cell and Molecular Biology, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8738.

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Accurate calculations of free energies for molecular association and solvation are important for the understanding of biochemical processes, and are useful in many pharmaceutical applications. In this thesis, molecular dynamics (MD) simulations are used to calculate thermodynamic properties for solvation and ligand binding.

The thermodynamic integration technique is used to calculate pK_a values for three aspartic acid residues in two different proteins. MD simulations are carried out in explicit and Generalized-Born continuum solvent. The calculated pK_a values are in qualitative agreement with experiment in both cases. A combination of MD simulations and a continuum electrostatics method is applied to examine pK_a shifts in wild-type and mutant epoxide hydrolase. The calculated pK_a values support a model that can explain some of the pH dependent properties of this enzyme.

Development of the linear interaction energy (LIE) method for calculating solvation and binding free energies is presented. A new model for estimating the electrostatic term in the LIE method is derived and is shown to reproduce experimental free energies of hydration. An LIE method based on a continuum solvent representation is also developed and it is shown to reproduce binding free energies for inhibitors of a malaria enzyme. The possibility of using a combination of docking, MD and the LIE method to predict binding affinities for large datasets of ligands is also investigated. Good agreement with experiment is found for a set of non-nucleoside inhibitors of HIV-1 reverse transcriptase.

Approaches for decomposing solvation and binding free energies into enthalpic and entropic components are also examined. Methods for calculating the translational and rotational binding entropies for a ligand are presented. The possibility to calculate ion hydration free energies and entropies for alkali metal ions by using rigorous free energy techniques is also investigated and the results agree well with experimental data.

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50

Chung, Salomon. "Effet d'un champ électrique sur la structure et la dynamique de suspensions colloïdales confinées : étude numérique par simulation". Thesis, Paris Est, 2017. http://www.theses.fr/2017PESC1059/document.

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Le travail présenté dans ce mémoire s'inscrit dans le cadre des études théoriques dedispersions colloïdales, ou suspensions de particules dont la taille varie du nanomètre aumicromètre. Dans ces milieux, les interactions entre les particules peuvent être moduléesen jouant par exemple sur leur composition superficielle, de même qu'il est possible demodifier l'environnement des colloïdes comme le solvant, le confinement du mélange et/ouéventuellement un champ extérieur pour influer sur leurs propriétés thermodynamiques.La modélisation-simulation permet alors de tester sur ordinateurcertains jeux de paramètres pouvant produire le phénomène souhaité,avant son éventuelle réalisation expérimentale.Ce travail se concentre sur cette étape préliminaire en considérant un mélange desphères dures dipolaires et apolaires, placé dans milieu confiné etsoumis à un champ électrique (magnétique pour des ferrocolloïdes).Dans une première étape, nous nous intéressons aux états d'équilibres du mélange,en étudiant par simulations Monte-Carlo un mélange symétrique en composition,non-additif et confiné entre deux murs éloignés.En comparant les résultats pour différentes densités et directions du champ extérieur,nous retrouvons certaines propriétés déjà observées pour des systèmes similaires.Nous commençons par la situation de référence sans champ où à faible densité,le mélange est monophasique et l'espèce dipolaire fuit les murs.L'augmentation de la densité favorise alors la séparation de phase et dans la phase richeen dipôles, l'espèce dipolaire mouille les murs.L'application d'un champ perpendiculaire aux murs favorise la stabilité du mélange malgrésa densité élevée et la non-additivité entre les deux espèces.En faisant croître ce champ, nous observons une structuration de l'espèce dipolaire,notamment près des murs ainsi que la formation de <> de dipôles dansla direction du champ.Enfin un champ parallèle aux murs provoque la démixtion du mélange dèsla plus faible densité considérée. Les dipôles fuient à nouveau les murs etnous observons de longues chaînes intriquées de dipôles.Dans une seconde étape, nous nous intéressons à la dynamique d'un mélange asymétrique encomposition et soumis à un champ. Nous combinons dans cette étudedes simulations Monte-Carlo et de dynamique moléculaire (Langevin).Le mélange est placé dans une boîte présentant un goulot d'étranglement afinde simuler un pore ouvert en contact avec un réservoir de particules,à travers une interface explicite. Le champ, perpendiculaire aux murs, sera appliquéau niveau du goulot d'étranglement afin d'y attirer les dipôles.Nous considérons d'abord un mélange peu dense afin que le cycle remplissage / vidagedu milieu confiné soit réversible. Dans le but d'accélérer ces cycles,l'intensité du champ est progressivement augmentée.Le remplissage en dipôles est effectivement plus rapide mais sa composition satureprématurément.Nous lançons ensuite une série de cycles avec des coefficients de frottement deLangevin croissants mais relativement petits afin de limiterla durée des simulations. Nous notons alors que les temps de remplissage oude vidage du pore varient linéairement en fonction du coefficient de frottementce qui nous permet d'estimer par extrapolation la durée d'un cycle pour les colloïdes.En jouant sur la non-additivité et la densité,nous parvenons à rendre les cycles irréversibles : selon l'application envisagée,l’irréversibilité pourra s'avérer utile ou devra être évitée.Nous terminons ce chapitre en estimant la variation de la durée des cycles avecla taille des colloïdes. Un modèle d'interaction entre colloïdes constitués pardes centres répulsifs en loi de puissance, uniformément répartis dans une sphèrenous permet de prévoir, moyennant des hypothèses sur les lois d'échelle,la variation des durées de remplissage ou de vidage pour des tailles allantde petits colloïdes aux dimensions quasi-moléculaires
The work presented in this dissertation is in the framework of the theoretical study ofcolloidal dispersions, i.e. suspensions of particles whose size varies from nanometers tomicrometers. In such a medium, the interactions between particles can be tuned through their surfacecomposition for instance. One may also modify the environment of the colloids:a specific solvent can be combined with confinement of the mixture andan external can field applied on it in order to tune its thermodynamic properties.Once a model of a physical system is defined, computer simulation can be used to explorea range of parameters to check if the sought phenomenon occurs, before carrying outany real experiment. This work focuses on this preliminary step: our model consists ofa mixture of dipolar and apolar hard spheres in a confined medium and subjected to anelectric field (or a magnetic one for ferrocolloids).In a first step, we use Monte Carlo simulation to study equilibrium states ofa binary mixture confined between distant walls,with symmetric composition of the two species having non additive interactions.By comparing the results of different densities and field directions,we recover some properties already observed for similar systems.In the reference state where the field is turned off, the mixture at low density is stableand we notice that the dipoles stay away from the walls.A denser mixture separates into two phases and in the dipoles rich one,the dipolar particles now wet the walls.When the mixture is subjected to a field perpendicular to the walls,it remains stable in spite of its high density and non additivity between unlike particles.Increasing the field induces a structuring of the dipolar component near the wallsand we observe column shaped clusters of dipoles along the direction of the field.Finally, the application of a field parallel to the walls separates the mixture,even at the lowest density we chose. Dipoles stay away from the walls and we observeentangled dipoles chains.In a second step we explore the dynamics of a mixture with asymmetric composition andsubjected to a field. We combine Monte Carlo and molecular dynamic (Langevin) simulationsin this study. The mixture is confined in a box with a bottleneck channel in order tosimulate an open pore exchanging particles with a reservoir through an explicit interface.The field which is perpendicular to the walls is applied in the bottleneck regionto attract dipoles there.We first consider a low density mixture such that the filling / emptying cycleof the pore is reversible.The intensity of the field is then increased to speed up the cycles.As expected, the dipoles fill the pore faster then. However their composition saturatesunder the maximum value found for a lower field.A series of cycles was performed with increasing Langevin damping coefficients but stilllow enough to reduced the computation time.We then notice that the filling or emptying duration is a linear function ofthe damping coefficient. The duration of a cycle for colloids is then obtained fromextrapolation.Combining non additivity and high enough density, we are able to make an irreversible cycle:depending on the application sought for, this irreversibility can be useful ormust be avoided.This chapter ends with the assessment of the duration of a cycle with respect tothe size of colloids. We use an interaction model between colloidal particles wherea colloid is uniformly made of repulsive centers following a power law.With some scaling law hypotheses, the duration of a filling or an emptying is estimated forsmall colloids down to nearly molecular dimensions

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Tesis sobre el tema "Interactive molecular simulations"

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