To see the other types of publications on this topic, follow the link: Protein simulation.
Dissertations / Theses on the topic 'Protein simulation'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'Protein simulation.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Park, Changmoon Goddard William A. "Protein design and simulation Part I. Protein design. Part II. Protein simulation /." Diss., Pasadena, Calif. : California Institute of Technology, 1993. http://resolver.caltech.edu/CaltechTHESIS:11112009-114142428.
Full textAbstract:
Thesis (Ph. D.)--California Institute of Technology, 1993. UM #93-25,374.Advisor names found in the Acknowledgements pages of the thesis. Title from home page. Viewed 01/15/2010. Includes bibliographical references.
2
Flöck, Dagmar. "Protein-protein docking and Brownian dynamics simulation of electron transfer proteins." [S.l. : s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=969418736.
Full text
3
Baskaran, Preetisri. "Computer simulation of protein superabsorbents." Thesis, Högskolan i Borås, Institutionen Ingenjörshögskolan, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:hb:diva-20927.
Full textAbstract:
The aim of this project is to develop superabsorbents from proteins in our case it is azygomycetes fungus, where the process of this fungus is studied experimentally in Universityof Borås. As a result of this experiment by-products of protein are produced and this project isabout the study to make use of such proteins as superabsorbing materials.The water absorbing capacity is computationally studied using Gibbs ensemble Monte Carlo(GEMC) simulations to determine the absorbing properties and to effectively improve theabsorbing capacity by using specific treatments, where this project focuses in using mesoscaleforce fields such as the MARTINI force field instead of atomistic force fields which wereused in studying the structure of the superabsorbents.For this purpose, the program code GEMMS is modified to make it read the desirable fileformats in order to perform the simulations. C++ is used here to code the program to read theGROMACS topology file (.top) for MARTINI force field instead of, as currently reading theatom type file (.atp) and the residue type file (.rtp) for the AMBER99 atomistic force field.
4
Mellor, Brett Lee. "Liquid Dielectric Spectroscopy and Protein Simulation." BYU ScholarsArchive, 2012. https://scholarsarchive.byu.edu/etd/3661.
Full textAbstract:
Protein electrical properties have been studied using dielectric relaxation measurements throughout the past century. These measurements have advanced both the theory and practice of liquid dielectric spectroscopy and have contributed to understanding of protein structure and function. In this dissertation, the relationship between permittivity measurements and underlying molecular mechanisms is explored. Also presented is a method to take molecular structures from the Protein Data Bank and subsequently estimate the charge distribution and dielectric relaxation properties of the proteins in solution. This process enables screening of target compounds for analysis by dielectric spectroscopy as well as better interpretation of protein relaxation data. For charge estimation, the shifted pKa values for amino acid residues are calculated using Poisson-Boltzmann solutions of the protein electrostatics over varying pH conditions. The estimated internal permittivity and estimated dipole moments through shifted pKa values are then calculated. Molecular dynamics simulations are additionally used to refine and approximate the solution-state conformation of the proteins. These calculations and simulations are verified with laboratory experiments over a large pH and frequency range (40 Hz to 110 MHz). The measurement apparatus is improved over previous designs by controlling temperature and limiting the electrode polarization effect through electrode surface preparation and adjustment of the cell's physical dimensions. The techniques developed in this dissertation can be used to analyze a wide variety of molecular phenomena experimentally and computationally, as demonstrated through various interactions amongst avidin, biotin, biotin-labeled and unlabeled bovine serum albumin, beta-lactoglobulin, and hen-lysozyme.
5
Naser, Md Abu. "Molecular dynamics simulation of protein adsorption." Thesis, Heriot-Watt University, 2008. http://hdl.handle.net/10399/2187.
Full text
6
Mitchell, Felicity. "Modelling protein flexibility using molecular simulation methods." Thesis, University of Manchester, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.525167.
Full text
7
Dantas, Gautam. "In silico protein evolution by intelligent design : creating new and improved protein structures /." Thesis, Connect to this title online; UW restricted, 2005. http://hdl.handle.net/1773/9236.
Full text
8
Badcoe, Ian Geoffrey. "Computer studies of protein folding." Thesis, University of Bristol, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.385585.
Full text
9
Zhang, Wei. "Computational simulation of biological systems studies on protein folding and protein structure prediction /." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file 2.84Mb, 184 p, 2005. http://wwwlib.umi.com/dissertations/fullcit/3181881.
Full text
10
Carpenter, Timothy S. "Simulation studies of the influenza M2 channel protein." Thesis, University of Oxford, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.504314.
Full text
11
Fischer, Bernhard Karl. "High throughput simulation methods for protein ligand docking." Karlsruhe : Forschungszentrum Karlsruhe, 2007. http://d-nb.info/985070374/34.
Full text
12
Wei, Shuai. "Protein-Surface Interactions with Coarse-Grain Simulation Methods." BYU ScholarsArchive, 2013. https://scholarsarchive.byu.edu/etd/3943.
Full textAbstract:
The interaction of proteins with surfaces is a major process involved in protein microarrays. Understanding protein-surface interactions is key to improving the performance of protein microarrays, but current understanding of the behavior of proteins on surfaces is lacking. Prevailing theories on the subject, which suggest that proteins should be stabilized when tethered to surfaces, do not explain the experimentally observed fact that proteins are often denatured on surfaces. This document outlines several studies done to develop a model which is capable of predicting the stabilization and destabilization of proteins tethered to surfaces. As the start point of the research, part of this research showed that the stability of five mainly-alpha, orthogonal-bundle proteins tethered to surfaces can be correlated to the shape of the loop region where the tether is placed and the free rotation ability of the part of proteins near surfaces. To test the expandability of the protein stability prediction pattern derived for mainly-alpha, orthogonal-bundle proteins, same analysis is performed for proteins from other structure motifs. Besides the study in these small two-state proteins, a further analysis of surface-induced change of folding mechanism is also studied with a multi-state lysozyme protein 7LZM. The result showed that by tethering a protein on a surface, the melting temperature of a part of the protein changed, which leads to an avoidance of the meta-stable state. Besides the change of folding mechanism, by tethering the lysozyme protein to a certain site, the protein could both keep a stable structure and a good orientation, allowing active sites to be available to other proteins in bulk solution. All the work described above are done with a purely repulsive surface model which was widely used to roughly simulate solid surfaces in protein microarrays. For a next-level understanding of protein-surface interactions, a novel coarse-grain surface model was developed, parameterized, and validated according to experimental results from different groups. A case study of interaction between lysozyme protein 7LZM and three types of surfaces with the novel model has been performed. The results showed that protein stabilities and structures are dependent on the types of surfaces and their different hydrophobicities. This result is consistent with previously published experimental work.
13
Richter, Barbara. "Combining simulation and experiment to extract protein dynamics." Thesis, University of Cambridge, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.612301.
Full text
14
Bruce, Neil John. "Investigating protein conformational change via molecular dynamics simulation." Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/investigating-protein-conformational-change-via-molecular-dynamics-simulation(17145939-f643-4b23-bbb9-029cf5489c15).html.
Full textAbstract:
Accumulation and aggregation of the 42-residue amyloid-[beta] (A[beta]) protein fragment, which originates from the cleavage of amyloid precursor protein by beta and gamma secretase, correlates with the pathology of Alzheimer's disease (AD). Possible therapies for AD include peptides based on the A[beta] sequence, and recently identified small molecular weight compounds designed to mimic these, that interfere with the aggregation of A[beta] and prevent its toxic effects on neuronal cells in culture. Here, we use molecular dynamics simulations to compare the mode of interaction of an active (LPFFD) and inactive (LHFFD) [beta]-sheet breaker peptide with an A[beta] fibril structure from solid state NMR studies. We found that LHFFD had a weaker interaction with the fibril than the active peptide, LPFFD, from geometric and energetic considerations, as estimated by the MM/PBSA approach. Cluster analysis and computational alanine scanning identified important ligand-fibril contacts, including a possible difference in the effect of histidine on ligand-fibril [pi]-stacking interactions, and the role of the proline residue establishing contacts that compete with those essential for maintenance of the inter-monomer [beta]-sheet structure of the fibril. Our results show that molecular dynamics simulations can be a useful way to classify the stability of docking sites. These mechanistic insights into the ability of LPFFD to reverse aggregation of toxic A[beta] will guide the redesign of lead compounds, and aid in developing realistic therapies for AD and other diseases of protein aggregation. We have also performed long explicit solvent MD simulations of unliganded amyloid fibril in three putative protonation states, in order to better understand the energetic and mechanical features of the fibril receptor. Over 100 ns MD simulations, the trajectories where fibril has Glu11 and Glu22 side-chains protonated exhibit the least deviation from the initial solid state NMR structures. Free energy calculations on these rajectories suggest that the weakest fibril interface lies in the lateral rather than transverse direction and that there is little dependence on whether the lateral interface is situated at the edge or middle of the fibril. This agrees with recent reported steered molecular dynamics calculations. Secondly, in an effort to improve the ability of atomistic simulation techniques to directly resolve protein tertiary structure from primary amino acid sequence, we explore the use of a molecular dynamics technique based on swarm intelligence, called SWARM-MD, to identify the native states of two peptides, polyalanine and AEK17, as well as Trp-cage miniprotein. We find that the presence of cooperative swarm interactions significantly enhanced the efficiency of molecular dynamics simulations in predicting native conformation. However, it also is evident that the presence of outlying simulation replicas can adversely impact correctly folded replica structures. By slowly removing the swarm potential after folding simulations, the negative effect of the swarm potential can be alleviated and better agreement with experiment obtained.
15
Ho, Sylvanna Sze Wan. "Molecular dynamics simulation studies of membrane protein biosensor components." Thesis, University of Oxford, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.442469.
Full text
16
Jiao, Yuanfang. "The development of accurate force fields for protein simulation." Diss., Kansas State University, 2012. http://hdl.handle.net/2097/13946.
Full textAbstract:
Doctor of PhilosophyDepartment of Chemistry
Paul E. Smith
Computer simulations have provided a wealth of information concerning a wide range of systems. The precision of computer simulation results depends on the degree of sampling (time scales) achieved, while the accuracy of the results (given sufficient sampling) depends on the quality of force field used. A force field provides a description of the energy for a system of interest. Recently, we have been developing a Kirkwood Buff (KB) force field for molecular dynamics simulations of biological systems. This force field is based on the KB Theory of solutions, emphasizing the accurate description of intermolecular interactions, and reasonably reproducing a range of other physical properties from experiment. In this approach simulation results in terms of KB integrals can be directly compared with experimental data through a KB analysis of the solution properties. The approach therefore provides a simple and clear method to test the capability of a force field. Here we firstly studied a series of alcohol-water mixtures in an attempt to validate the transferability and additivity of the force field. A general fluctuation theory was applied to investigate the properties of these systems, and to compare with computer simulation results. The possible effects of cosolvents on peptides and proteins were then investigated using N-methylacetamide as model for the peptide backbone and urea as cosolvent. A possible explanation for the urea denaturation of protein structure was provided using a thermodynamics point of view involving transfer free energies and preferential interactions obtained from the KB integrals. Finally, potentials for protein backbone and sidechain torsions were developed by fitting to quantum mechanical calculations and NMR data. Simulations of a variety of peptides and proteins in aqueous solutions were then performed to demonstrate the overall reliability of the force field.
17
Taylor, Richard David. "Novel simulation methods for flexible docking." Thesis, University of Southampton, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.368873.
Full text
18
Vagedes, Peter. "Simulation of enzyme reactions the influence of protonation on catalysis and on protein protein association /." [S.l. : s.n.], 2001. http://www.diss.fu-berlin.de/2001/49/index.html.
Full text
19
Soni, Ravi. "Computer-aided modeling and simulation of molecular systems and protein secondary structure prediction." Ohio : Ohio University, 1993. http://www.ohiolink.edu/etd/view.cgi?ohiou1176235817.
Full text
20
Huang, Zheng. "Computer-aided modeling and simulation of molecular systems and protein (WT-bGH) structure minimization." Ohio : Ohio University, 1995. http://www.ohiolink.edu/etd/view.cgi?ohiou1179347691.
Full text
21
Rabenstein, Björn. "Monte Carlo methods for simulation of protein folding and titration." [S.l. : s.n.], 2000. http://www.diss.fu-berlin.de/2000/124/index.html.
Full text
22
Marchut, Alexander Joseph. "Simulation of Polyglutamine Aggregation With An Intermediate Resolution Protein Model." NCSU, 2006. http://www.lib.ncsu.edu/theses/available/etd-01062006-142134/.
Full textAbstract:
The pathological manifestation of nine hereditary neurodegenerative diseases including Huntington's disease is the presence within the brain of aggregates of disease-specific proteins that contain polyglutamine tracts longer than a critical length. The molecular level mechanisms by which these proteins aggregate are still unclear. In an effort to shed light on this important phenomenon, we are investigating the aggregation of model fibril-forming peptides using molecular-level computer simulation. A simplified model of polyglutamine, the protein that is known to form fibrils (ordered aggregates of proteins in beta-sheet conformations) in the brains of victims of Huntington's disease, has been developed. This model accounts for the most important types of intra- and inter-molecular interactions - hydrogen bonding and hydrophobic interactions - while allowing the folding process to be simulated in a reasonable time frame. The model utilizes discontinuous potentials such as hard spheres and square wells in order to take advantage of discontinuous molecular dynamics (DMD), a fast simulation technique that is very computationally efficient. DMD is used to examine the folding and aggregation of systems of model polyglutamine peptides ranging in size from isolated peptides to 96 peptides. In our simulations we observe the spontaneous formation of aggregates and annular structures that are made up of beta sheets starting from random configurations of random coils. The effect of chain length on the behavior of our model peptides was examined by simulating the folding of isolated polyglutamine peptides 16, 32, and 48 residues long and the folding and aggregation of systems of twenty-four model polyglutamine peptides 16, 32, 36, 40, and 48 residues long. In our multi-peptide simulations we observed that the optimal temperature for the formation of beta sheets increases with chain length up to 36 glutamine residues but not beyond. Our finding of this critical chain length of 36 glutamine residues is interesting because a critical chain length of 37 glutamine residues has been observed experimentally.
23
Hopkins, Sawyer S. "Examination of nonlocal screening effects on protein crystallization." Thesis, Kansas State University, 2017. http://hdl.handle.net/2097/35376.
Full textAbstract:
Master of ScienceDepartment of Physics
Jeremy Schmit
Over twenty percent of amino acids are ionized under biological conditions, and the subsequent electrostatic interactions have substantial effect on protein crystallization, binding, catalyzation, and recognition. These electrostatics along with other intermolecular forces create a delicate balancing act of repulsive and attractive forces. This thesis explores the effects of electrostatics on the formation of dense ordered structures. In dense protein aggregates the repulsive electrostatics are dominated by the entropic cost of compressing salt ions in the electrostatic screening layer. A non-local electrostatic interaction was derived to describe this behavior, and was used to examine the interplay of attractive energies and repulsive entropy on protein colloid stability and the crystallization process. Using a simple analytical model it was predicted that the derived electrostatic effects describe a finite window in phase space in which crystallization can occur. This simple model was expanded upon via computational methods simulating hard spherical particles aggregating under short-ranged attractive interactions and the repulsive electrostatics. From the computational simulations phase and dynamical data was extracted to confirmed the initial insight of the analytical model. The simulations also introduced new information not described by the simple model, most notably a metastable amorphous phase caused by the competition of energies and entropies.
24
Whitehead, L. "Computer simulation of biological membranes and membrane bound proteins." Thesis, University of Southampton, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.297412.
Full text
25
Pinska, Adrianna. "Addition of flexible linkers to GPU-accelerated coarse-grained simulations of protein-protein docking." Thesis, Faculty of Science, 2019. http://pubs.cs.uct.ac.za/archive/00001307/.
Full textAbstract:
Multiprotein complexes are responsible for many vital cellular functions, and understanding their formation has many applications in medical research. Computer simulation has become a valuable tool in the study of biochemical processes, but simulation of large molecular structures such as proteins on a useful scale is computationally expensive. A compromise must be made between the level of detail at which a simulation can be performed, the size of the structures which can be modelled and the time scale of the simulation. Techniques which can be used to reduce the cost of such simulations include the use of coarse-grained models and parallelisation of the code. Parallelisation has recently been made more accessible by the advent of Graphics Processing Units (GPUs), a consumer technology which has become an affordable alternative to more specialised parallel hardware.
We extend an existing implementation of a Monte Carlo protein-protein docking simulation using the Kim and Hummer coarse-grained protein model [1] on a heterogeneous GPU-CPU architecture [2]. This implementation has achieved a significant speed-up over previous serial implementations as a result of the efficient parallelisation of its expensive non-bonded potential energy calculation on the GPU.
Our contribution is the addition of the optional capability for modelling flexible linkers between rigid domains of a single protein. We implement additional Monte Carlo mutations to allow for movement of residues within linkers, and for movement of domains connected by a linker with respect to each other. We also add potential terms for pseudo-bonds, pseudo-angles
and pseudo-torsions between residues to the potential calculation, and include additional residue pairs in the non-bonded potential sum. Our flexible linker code has been tested, validated and benchmarked. We find that the implementation is correct, and that the addition of the linkers does not significantly impact the performance of the simulation.
This modification may be used to enable fast simulation of the interaction between component proteins in a multiprotein complex, in configurations which are constrained to preserve particular linkages between the proteins. We demonstrate this utility with a series of simulations of diubiquitin chains, comparing the structure of chains formed through all known linkages between two ubiquitin monomers. We find reasonable agreement between our simulated structures and experimental data on the characteristics of diubiquitin chains in solution.
26
Razavi, Majarashin Asghar. "MARKOV STATE MODELS AND THEIR APPLICATIONS IN PROTEIN FOLDING SIMULATION, SMALL MOLECULE DESIGN, AND MEMBRANE PROTEIN MODELING." Diss., Temple University Libraries, 2015. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/362098.
Full textAbstract:
ChemistryPh.D.
This dissertation is focused on the application of Markov State Models on protein folding and designing of small drug-like molecules, as well as application of computational tools on the study of biological processes. The central focus of protein folding is to understand how proteins obtain their unique three-dimensional structure from their aminoacid sequences. The function of protein critically depends on its three- dimensional structure; hence, any internal (such as mutations) or external (such as high temperature) perturbation that obstructs three-dimensional structure of a protein will also interfere with its function. Many diseases are associated with inability of protein to form its unique structure. For example, sickle cell anemia is caused by a single mutation that changes glutamic acid to valine. Molecular dynamics (MD) simulations could be utilized to study protein folding and effects of perturbations on protein energy landscape; however, due to its inherent atomic resolution, MD simulations usually provide enormous amount of data even for small proteins. A thorough analysis and extraction of desired information from MD provided data could be extremely challenging and is well beyond human comprehension. Markov state models (MSMs) are proved to be apt for the analysis of large scale random processes and equilibrium conditions, hence it could be applied for protein folding studies. MSMs can be used to obtain long timescale information from short timescale simulations. In other words, the combination of many short simulations and MSMs is a powerful technique to study the folding mechanism of many proteins, even the ones with folding times over millisecond. This dissertation is centered on the use of MSMs and MD simulation in understanding protein folding and biological processes and is constructed as the following. The first chapter provides a brief introduction into MD simulation and the different techniques that could be used to facilitate simulations. Protein folding and its challenges are also discussed in chapter one. Finally, chapter one ends with describing MSMs and technical aspects of building them for protein folding studies. Chapter two is focused on using MD simulations and MSMs to design small protein like molecules to prevent biofilm propagation by disrupting its lifecycle. The biofilm lifecycle and strategy for its interruption is described first. Then, the designed molecules and their conformational sampling by MD simulations are explained. Next, the application of MSMs in obtaining and comparing equilibrium population of all designs are discussed. At the end of chapter two, the molecular descriptions of best designs are explained. Chapter three is focused on the effects of mutations on the energy landscape of a sixteen residue protein from c-terminal hairpin of protein G, GB1. Three mutations, tz4, tz5, and tz6 are discussed, and their folding rates and folding mechanisms are compared with wild-type GB1 using MSMs built from a significantly large MD simulation data set (aggregating over 9 millisecond). Finally, chapter four is focused on the application of MD simulations on understanding the selectivity of Na,K-ATPase, a biologically critical protein that transports sodium ions outside and potassium ions inside against their concentration gradient in almost all eukaryotic cells. Multiple MD approaches, including metadynamics and free energy perturbation methods are used to describe the origins of selectivity for Na,K-ATPase.
Temple University--Theses
27
Fischer, Bernhard Karl [Verfasser]. "High throughput simulation methods for protein ligand docking / Bernhard Karl Fischer." Karlsruhe : Forschungszentrum Karlsruhe, 2007. http://d-nb.info/985070374/34.
Full text
28
Duan, Jianxin. "Protein folding, stability and recognition /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7140-098-2/.
Full text
29
Gunnerson, Kim Noreen. "Computer simulation studies of molecular interactions by application of classical molecular dynamics /." Thesis, Connect to this title online; UW restricted, 2007. http://hdl.handle.net/1773/8668.
Full text
30
Engström, Mathias, and Erik Olby. "Evaluating Response Images From Protein Quantification." Thesis, Uppsala universitet, Institutionen för biologisk grundutbildning, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-416108.
Full textAbstract:
Gyros Protein Technologies develops instruments for automated immunoassays. Fluorescent antibodies are added to samples and excited with a laser. This results in a 16-bit image where the intensity is correlated to concentration of bound antibody. Artefacts may appear on the images due to dust, fibers or other problems, which affect the quantification. This project seeks to automatically detect such artifacts by classifying the images as good or bad using Deep Convolutional Neural Networks (DCNNs). To augment the dataset a simulation approach is used and a simulation program is developed that generates images based on developed simulation models. Several classification models are tested as well as different techniques used for training. The highest performing classifier is a VGG16 DCNN, pre-trained on simulated images, which reaches 94.8% accuracy. There are many sub-classes in the bad class, and many of these are very underrepresented in both the training and test datasets. This means that not much can be said of the classification power of these sub-classes. The conclusion is therefore that until more of this rare data can be collected, focus should lie on classifying the other more common examples. Using the approaches from this project, we believe this could result in a high performing product.
31
Kolmodin, Karin. "Computer Simulation of Protein Tyrosine Phosphatase Reaction Mechanisms and Dihydrofolate Reductase Inhibition." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : [Univ.-bibl. [distributör]], 2001. http://publications.uu.se/theses/91-554-5148-9/.
Full text
32
Mistry, Shailesh Lallubhai. "Mathematical modelling and computer simulation of aqueous two-phase continuous protein extraction." Thesis, University of Reading, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.327153.
Full text
33
Loganathan, Narasimhan. "Adsorption of protein bound uremic toxins in zeolites : a molecular simulation study." Aix-Marseille 1, 2010. http://www.theses.fr/2010AIX11120.
Full textAbstract:
Le paracrésol sous sa forme libre est une toxine urémique causant des dommages cellulaires très importants qui peuvent conduire E1 des arrêts cardiaques. Le traitement de l'insuffisance rénale repose principalement sur l‘utilisation de la dialyse. Il s'avère cependant que ce procédé ne permet pas une élimination efficace de la toxine. Une alternative serait d'utiliser des zéolithes afin de piéger la molécule pour ensuite l'éliminer. Ce travail de thèse présente une étude théorique de l‘adsorption du paracrésol et de l'eau dans les zéolithes silicalite-1 et faujasites NaY. Les simulations ont été réalisées par la technique Monte Carlo dans les ensembles grand-canonique et canonique à une température de 37°C (310 K). Les résultats montrent qu‘un effet coopératif interviendrait entre les deux molécules lors de la coadsorption dans la silicalite-1. L‘étude détaillée des interactions énergétiques intermoléculaires semble confirmer cette hypothèse. Les simulations montrent que le mécanisme d'adsorption dans la faujasite est quelque peu différentThe paracresol as a free molecule is a uremic toxin that may cause critical cell damages which can eventually lead to heart failures. The treatment of renal insufficiency is essentially based on the utilisation of the dialysis techniques. However, it appears that, this process does not allow the effective elimination of the molecule. A possible alternative would be to use zeolites to sequestrate the molecule in order to eliminate it. This PhD thesis presents a theoretical investigation of the adsorption of paracresol and water in the silicalite-1 and faujasite NaX and NaY zeolites. The computer simulations were performed using the Monte Carlo technique in both the grand-canonical and canonical ensembles at a temperature of 98. 6° (310 K). The results show that, a cooperative effect could appear between both molecules during the coadsorption in silicalite-1. The detailed study of the energetic intermolecular interactions seems to confirm this hypothesis. The simulations show that, the mechanism of adsorption in the faujasite zeolites is somewhat different
34
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.
Full textAbstract:
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 511/521Drepanocytosis 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
35
Chen, Wei. "Molecular dynamics simulations of binding, unfolding, and global conformational changes of signaling and adhesion molecules." Diss., Atlanta, Ga. : Georgia Institute of Technology, 2009. http://hdl.handle.net/1853/28118.
Full textAbstract:
Thesis (M. S.)--Mechanical Engineering, Georgia Institute of Technology, 2009.Committee Chair: Zhu, Cheng; Committee Member: Harvey, Stephen; Committee Member: Hud, Nicholas; Committee Member: Zamir, Evan; Committee Member: Zhu, Ting.
36
Sawada, Ryusuke, Runcong Ke, Toshiyuki Tsuji, Masashi Sonoyama, and Shigeki Mitaku. "Ratio of membrane proteins in total proteomes of prokaryota." THE BIOPHYSICAL SOCIETY OF JAPAN, 2007. http://hdl.handle.net/2237/9298.
Full text
37
Hirst-Dunton, Thomas Alexander. "Using molecular simulations to parameterize discrete models of protein movement in the membrane." Thesis, University of Oxford, 2015. https://ora.ox.ac.uk/objects/uuid:893568e9-696f-47e7-8495-59ecfb810459.
Full textAbstract:
The work presented in this thesis centres on the development of a work-flow in which coarse-grained molecular dynamics (MD) simulations of a planar phospholipid bilayer, containing membrane proteins, is used to parameterize a larger-scale simplified bilayer model. Using this work-flow, repeat simulations and simulations of larger systems are possible, better enabling the calculation of bulk statistics for the system. The larger-scale simulations can be run on commercial hardware, once the initial parameterization has been performed. In the simplified representation, each protein was initially only represented by the position of its centre of mass and later with the inclusion of its orientation. The membrane protein used throughout most of this work was the bacterial outer membrane protein NanC, a member of the KdgM family of proteins. To parameterize the motion and interaction of proteins using MD, the potential of mean force (PMF) for the pairwise association of two proteins in a bilayer was calculated for a variety of orientational combinations, using a modified umbrella sampling procedure. The relative orientations chosen represented extreme examples of the contact regimes between the two proteins: they approximately corresponded to maxima and minima of the solvent inaccessible surface area, calculated when the proteins were in contact. These PMFs showed that there was a correlation between the buried surface area and the depth of the potential well in the PMF; this is something that, to date, has only been observed in these relatively-'featureless' membrane proteins (but is seen in globular proteins), where the effect of the interactions with lipids in the bilayer plays a larger role. Features in the PMF were observed that resulted from the preferential organization of lipids in the region between the two proteins. These features were small wells in the PMF, which occurred at protein separations that corresponded to the intervening lipids being optimally packed between the proteins. This result further highlighted the role that the lipids in the bilayer played in the interaction between the NanC proteins. The simplified bilayer model was parameterized using the PMFs and the relationship between buried surface area and potential well depth. The initial model included only the proteins' positions. A series of Monte Carlo simulations were performed in order to compare the system behaviour to that of an equivalent MD simulation. Initially, the MD simulation and our parameterized model did not show a good agreement, so a Monte Carlo scheme that incorporated cluster-based movements was implemented. The agreement between the MD simulation and the simulations of our model using the cluster-based scheme, when comparing diffusive and clustering behaviour, was good. Including the orientation-dependent features of the parameterization resulted in the emergence of behaviour that was not clearly detectable in the MD simulation. Finally, attempts were made to parameterize the model using PMFs for the association of rhodopsin from the literature. Rhodopsin was a much more complicated protein to represent: there was not a clear correlation between surface area and the features of the PMF, and the geometry of the interaction between two rhodopsins was more complicated. Simulations of the 'rows-of-dimers' system of rhodopsin, observed in disc membranes, was not entirely well represented by the model; for such a closely packed system, where the number of lipids is much closer to the number of proteins, the use of an implicit-lipid model meant that the effect of the reduced lipid mobility was not adequately captured. However, the model accurately captures the orientational composition of the system. Future work should be focussed on incorporating explicit representations of the lipid in the system so that the behaviour of close-packed systems are better represented.
38
Wei, Aoran. "Adsorption of protein on a au surface studied by all-atom atomistic simulations." The Journal of Physical Chemistry C, 2016. http://hdl.handle.net/1993/31807.
Full textAbstract:
In this work, the adsorption of protein on Au surface coated by self-assembled monolayers (SAMs) of alkanethiol chains is studied by molecular dynamics simulations with an all-atom model. Particularly, a more realistic embedded-atom method potential has been used to characterize the Au-Au interactions in the system as compared to previous studies. With this all-atom model, many experimental observations have been reproduced from the simulations. It is found that the SAMs have the lowest adsorption energy on Au (111) surface where the alkanethiol chains form a well-ordered (√3x√3) R30° triangular lattice at 300 K. Furthermore, it is confirmed that carboxyl-terminated SAMs are more effective to absorb proteins than the methyl-terminated SAMs. Base on the simulation results, we propose that the experimentally observed aggregation of protein-Au nanoparticle conjugates is mainly due to the electrostatic interactions between protein amino acids and carboxyl-terminated SAMs from multiple Au surfaces.October 2016
39
Ullmann, G. Matthias. "Simulation and analysis of docking and molecular dynamics of electron transfer protein complexes." [S.l. : s.n.], 1998. http://darwin.inf.fu-berlin.de/1998/23/index.html.
Full text
40
Javidialesaadi, Abdolreza. "Computer Simulations of Titin I27 and Knotted Protein Remodeling by Clp Biological Nanomachines." University of Cincinnati / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1523628577990709.
Full text
41
Budi, Bunarta Hendra (Akin), and akin budi@rmit edu au. "On the effects of external stresses on protein conformation." RMIT University. School of Applied Sciences, 2006. http://adt.lib.rmit.edu.au/adt/public/adt-VIT20061116.123431.
Full textAbstract:
The use of electromagnetic devices such as microwave ovens and mobile phones has certainly brought convenience to our lives. At the same time, the proliferation of said devices has increased public awareness of the potential health hazards. It is generally assumed that there is little or no risk associated with the use of electromagnetic devices, based on the small amount of power associated with those devices. However, case studies on animals indicate that the risk cannot be entirely ruled out. It has long been known that proteins are sensitive to stress, arising from various sources such as temperature, chemical, pressure, and changes in pH condition. In all of these cases, the protein exhibits clear signs of damage and distress, which range from slight unfolding to complete loss of structure. Frequently, the damage to the protein is alleviated by refolding, either by itself or by the aid of molecular chaperones. However, if the damage to the protein is too great, the protein will generally undergo proteolysis. Opinion has been divided over the implication of prolonged use of electromagnetic devices to human health. Studies conducted on animals so far have given conflicting results. The studies on the separate components, electric and magnetic fields, also give inconclusive results. This indicates that our understanding on how electric and magnetic fields interact with biological matter is incomplete. In this project, we use molecular dynamics to explore the behaviour of two forms of insulin chain-B, isolated and monomeric (in the presence of chain-A with all disulfide bonds intact), at ambient conditions and under the influence of various stress. Specifically, we focus our attention to thermal stress and electric field stress. The electric field stress considered in this study takes several forms: static and oscillating with three different frequencies. These fields have strength ranging from 1806 V/m to 109 V/m. By performing molecular dynamics simulations totalling over 500 ns, we have gained valuable insights into the effects of elevated temperature and electric field on insulin chain-B. We observed differences in the damage mechanisms by the application of static electric field and oscillating field. The application of static fields restricts the conformational freedom of a protein, whereas the application of oscillating fields increases the mobility and flexibility of the protein, similar to the effect of thermal stress. Both of these interfere with the normal behaviour of a protein. We have also observed frequency-dependent effects, with low frequency fields having static field-like characteristics in damage mechanism.
42
Beugelsdijk, Alex. "Understanding amyloid fibril growth through theory and simulation." Thesis, Kansas State University, 2014. http://hdl.handle.net/2097/18117.
Full textAbstract:
Master of ScienceBiochemistry and Molecular Biophysics
Jianhan Chen
Proteins are fundamental building blocks of life in an organism, and to function properly, they must adopt an appropriate three-dimensional conformation or conformational ensemble. In protein aggregation diseases, proteins misfold to incorrect structures that allow them to join together and form aggregates. A wide variety of proteins are involved in these aggregation diseases and there are multiple theories of their disease mechanism. However, a common theme is that they aggregate into filamentous structures. Therapies that target the process by which the aggregating proteins assemble into these similar fibril-like structures may by effective at countering aggregation diseases. This requires models that can accurately describe the assembly process of the fibrils. An analytical theory was recently described where fibrils grow by the templating of peptides onto an existing amyloid core and the kinetics of the templating process is modeled as a random walk in the backbone hydrogen bonding space. In this thesis, I present my work integrating molecular simulation with this analytical model to investigate the dependence of fibril growth kinetics on peptide sequence and other molecular details. Using the Aβ16-22 peptide as a model system, we first calculate the rate matrix of transitions among all possible hydrogen bonding microscopic states using numerous short-time simulations. These rates were then used to construct a kinetic Monte Carlo model for simulations of long-timescale fibril growth. The results demonstrate the feasibility of using such a theory/simulation framework for bridging the significant gap between fibril growth and simulation timescales. At the same time, the study also reveals some limits of describing the fibril growth as a templating process in the backbone hydrogen bonding space alone. In particular, we found that dynamics in nonspecifically bound states must also be considered. Possible solutions to this deficiency are discussed at the end.
43
Karjalainen, Eeva-Liisa. "The choreography of protein vibrations : Improved methods of observing and simulating the infrared absorption of proteins." Doctoral thesis, Stockholms universitet, Institutionen för biokemi och biofysik, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-60415.
Full textAbstract:
The work presented in this thesis has striven toward improving the capability to study proteins using infrared (IR) spectroscopy. This includes development of new and improved experimental and theoretical methods to selectively observe and simulate protein vibrations. A new experimental method of utilising adenylate kinase and apyrase as helper enzymes to alter the nucleotide composition and to perform isotope exchange in IR samples was developed. This method enhances the capability of IR spectroscopy by enabling increased duration of measurement time, making experiments more repeatable and allowing investigation of partial reactions and selected frequencies otherwise difficult to observe. The helper enzyme mediated isotope exchange allowed selective observation of the vibrations of the catalytically important phosphate group in a nucleotide dependent protein such as the sarcoplasmic reticulum Ca2+-ATPase. This important and representative member of P-type ATPases was further investigated in a different study, where a pathway for the protons countertransported in the Ca2+-ATPase reaction cycle was proposed based on theoretical considerations. The transport mechanism was suggested to involve separate pathways for the ions and the protons. Simulation of the IR amide I band of proteins enables and supports structure-spectra correlations. The characteristic stacking of beta-sheets observed in amyloid structures was shown to induce a band shift in IR spectra based on simulations of the amide I band. The challenge of simulating protein spectra in aqueous medium was also addressed in a novel approach where optimisation of simulated spectra of a large set of protein structures to their corresponding experimental spectra was performed. Thereby, parameters describing the most important effects on the amide I band for proteins could be determined. The protein spectra predicted using the optimised parameters were found to be well in agreement with experiment.At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 5: Manuscript.
44
Merz, Dale R. Jr. "Molecular simulations uncover the nanomechanics of heat shock protein (70 kDa) & Indentation simulations of microtubules reveal katanin severing insights." University of Cincinnati / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1583154342504106.
Full text
45
Druart, Karen. "Défis algorithmiques pour les simulations biomoléculaires et la conception de protéines." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLX080/document.
Full textAbstract:
Le dessin computationnel de protéine, ou CPD, est une technique qui permet de modifier les protéines pour leur conférer de nouvelles propriétés, en exploitant leurs structures 3D et une modélisation moléculaire. Pour rendre la méthode de plus en plus prédictive, les modèles employés doivent constamment progresser. Dans cette thèse, nous avons abordé le problème de la représentation explicite de la flexibilité du squelette protéique. Nous avons développé une méthode de dessin "multi-états", qui se base sur une bibliothèque discrète de conformations du squelette, établie à l'avance. Dans un contexte de simulation Monte Carlo, le paysage énergétique d'une protéine étant rugueux, les changements de squelettes ne peuvent etre acceptés que moyennant certaines précautions. Aussi, pour explorer ces conformations, en même temps que des mutations et des mouvements de chaînes latérales, nous avons introduit un nouveau type de déplacement dans une méthode Monte Carlo existante. Il s'agit d'un déplacement "hybride", où un changement de squelette est suivi d'une courte relaxation Monte Carlo des chaînes latérales seules, après laquelle un test d'acceptation est effectué. Pour respecter une distribution de Boltzmann des états, la probabilité doit avoir une forme précise, qui contient une intégrale de chemin, difficile à calculer en pratique. Deux approximations sont explorées en détail: une basée sur un seul chemin de relaxation, ou chemin "générateur" (Single Path Approximation, ou SPA), et une plus complexe basée sur un ensemble de chemins, obtenus en permutant les étapes élémentaires du chemin générateur (Permuted Path Approximation, ou PPA). Ces deux approximations sont étudiées et comparées sur deux protéines. En particulier, nous calculons les énergies relatives des conformations du squelette en utilisant trois méthodes différentes, qui passent réversiblement d'une conformation à l'autre en empruntent des chemins très différents. Le bon accord entre les méthodes, obtenu avec de nombreuses paramétrisations différentes, montre que l'énergie libre se comporte bien comme une fonction d'état, suggérant que les états sont bien échantillonnés selon la distribution de Boltzmann. La méthode d'échantillonnage est ensuite appliquée à une boucle dans le site actif de la tyrosyl-ARNt synthétase, permettant d'identifier des séquences qui favorisent une conformation, soit ouverte, soit fermée de la boucle, permettant en principe de contrôler ou redessiner sa conformation. Nous décrivons enfin un travail préliminaire visant à augmenter encore la flexibilité du squelette, en explorant un espace de conformations continu et non plus discret. Ce changement d'espace oblige à restructurer complètement le calcul des énergies et le déroulement des simulations, augmente considérable le coût des calculs, et nécessite une parallélisation beaucoup plus agressive du logiciel de simulationComputational protein design is a method to modify proteins and obtain new properties, using their 3D structure and molecular modelling. To make the method more predictive, the models need continued improvement. In this thesis, we addressed the problem of explicitly representing the flexibility of the protein backbone. We developed a "multi-state" design approach, based on a small library of backbone conformations, defined ahead of time. In a Monte Carlo framework, given the rugged protein energy landscape, large backbone motions can only be accepted if precautions are taken. Thus, to explore these conformations, along with sidechain mutations and motions, we have introduced a new type of Monte Carlo move. The move is a "hybrid" one, where the backbone changes its conformation, then a short Monte Carlo relaxation of the sidechains is done, followed by an acceptation test. To obtain a Boltzmann sampling of states, the acceptation probability should have a specific form, which involves a path integral that is difficult to calculate. Two approximate forms are explored: the first is based on a single relaxation path, or "generating path" (Single Path Approximation or SPA). The second is more complex and relies on a collection of paths, obtained by shuffling the elementary steps of the generating path (Permuted Path Approximation or PPA). These approximations are tested in depth and compared on two proteins. Free energy differences between the backbone conformations are computed using three different approaches, which move the system reversibly from one conformation to another, but follow very different routes. Good agreement is obtained between the methods and a wide range of parameterizations, indicating that the free energy behaves as a state function, as it should, and strongly suggesting that Boltzmann sampling is verified. The sampling method is applied to the tyrosyl-tRNA synthetase enzyme, allowing us to identify sequences that prefer either an open or a closed conformation of an active site loop, so that in principle we can control, or design the loop conformation. Finally, we describe preliminary work to make the protein backbone fully flexible, moving within a continuous and not a discrete space. This new conformational space requires a complete reorganization of the energy calculation and Monte Carlo simulation scheme, increases simulation cost substantially, and requires a much more aggressive parallelization of our software
46
Danielsson, Emma. "Towards a better understanding of protein structures : assessing the sulfur bridge in Cystine through photofragmentation." Thesis, Uppsala universitet, Materialteori, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-416437.
Full textAbstract:
This work aims to investigate the fragmentation of an ionized Cystine molecule, as simulated in the framework of molecular dynamics and quantum mechanics. Cystine is viewed as a model system for larger sets of peptides -- ultimately contributing to the understanding of protein photofragmentation, which is crucial for determining the structure of a protein using new methods. The analysis software was written in Python, partly in conjunction with another student. The photofragmentation of the molecule is analyzed in terms of bond integrity versus time and mass-to-charge ratios for the resulting fragments. Generally, the molecule disintegrates into more and smaller fragments the higher the degree of ionization is.I det föreliggande arbetet undersöks fragmenteringen av en joniserad molekyl Cystin, som simulerats medelst molekyldynamik och kvantmekanik. Cystin betraktas som ett modellsystem för större peptidstrukturer -- något som i längden kan bidra till större förståelse för fotofragmentering av proteiner, vilket i sin tur är avgörande inom nya metoder för strukturbestämning. Analysprogrammet skrevs i Python och delvis i samarbete med en annan student. Molekylens fotofragmentering analyseras med avseende på bindningsintegritet över tid, samt mass-laddningskvot hos de resulterande fragmenten. I allmänhet sönderfaller molekylen till fler och mindre fragment ju högre joniseringsnivån är.
47
Mauk, Andrew W. "A new modeling protocol for G-protein coupled receptors : molecular simulation of phospholipid assemblies." Thesis, Georgia Institute of Technology, 1996. http://hdl.handle.net/1853/11033.
Full text
48
Hosseini, Seyed Ali. "Modeling protein dynamics and protein-drug interactions with Monte Carlo based techniques." Doctoral thesis, Universitat de Barcelona, 2015. http://hdl.handle.net/10803/294730.
Full textAbstract:
A complete understanding of complex formation between proteins and ligands, a crucial matter for pharmacology and, more in general, in biomedicine, requires a detailed knowledge of their static and dynamic atomic interactions. The main objective of this thesis is to test recent developments in conformational sampling techniques in providing such a dynamical view. We aim at developing new protocols and methods for such a study. Moreover, we want to show how its application can aid in addressing existing problems in the biophysics of protein ligand interactions. Moreover, we apply and refine novel computational approaches aiming at a comprehensive description of the protein and protein-ligand energy landscape, progressing into the rational design of new inhibitors for particular targets. We provide here a summary of the main results.
PELE was used for induce fit docking in protein kinases, mammalian target of rapamycin (mTOR) and BCL-2 family protein, particularly MCL-1 protein. Results produced a detailed atomic description of the binding modes of ligand/drug to the selected target. Overall, these results provide new data to understand the mechanism of action of these molecules, and provide new structural data that will allow the development of more Specific inhibitors for cancer treatments. Importantly, we demonstrate the critical role of sampling the protein-ligand dynamics in order to improve the docking score. Moreover, the findings reported here clearly shown the capabilities of PG (and its derivatives) for use in particular apoptotic targets.
Following the previous goal, we aim at the implementation of the atomic detailed knowledge into the rational design of new inhibitors, aiming to enhance specificity and binding strength. Motivated by our success with validation studies (applied to several systems for protein-ligand interaction and induce fit procedure) we attempted to design a new inhibitor for a specific target. For doing so, we used the system from our second study: Molecular interactions of prodiginines with the BH3 domain of BCL-2 family members. We have shown how PELE can be used in effectively design improved compounds with significant better docking results.
The PELE was applied to steroid Nuclear Receptors to unbiased simulations, where substrate/ligands were placed in the active site, to freely move through the protein and finding the channels, or outside the receptors allowed ligand to freely explore the protein surface. In this study, we demonstrated the applicability of the PELE method in solving relevant biophysical problems. In particular, using PELE we introduced a new structural and dynamic paradigm for ligand binding in steroid nuclear receptors.
Using PELE, we create a protocol involving sequence comparison and allatom protein-ligand induced fit simulations to predict PR resistance at the molecular level. We introduced a significant advance in predicting the affinity of different drugs against HIV-1 protease with several mutations. This study shows how computational techniques are capable of quantitatively discriminating resistance variants of HIV-1 protease. This application is fully automated and installed on PELE web server.
Beside these main objectives based on methods application, we aim to add methodological improvements derived from the application and validation studies. We performed method development and studied PELE protocols to model long-time protein dynamics by means of normal mode perturbation and constrained minimization. New backbone perturbation combined with normal modes increased the capability of PELE method to explore local dynamics and large conformational changes.
49
Dibenedetto, Domenica [Verfasser]. "Predicting conformational ensembles of the intrinsically disordered protein alpha-synuclein via molecular simulation / Domenica Dibenedetto." Aachen : Hochschulbibliothek der Rheinisch-Westfälischen Technischen Hochschule Aachen, 2014. http://d-nb.info/1052303420/34.
Full text
50
Weber, Jeffrey. "Coarse Grained Monte Carlo Simulation of the Self-Assembly of the HIV-1 Capsid Protein." Honors in the Major Thesis, University of Central Florida, 2014. http://digital.library.ucf.edu/cdm/ref/collection/ETH/id/1654.
Full textAbstract:
In this study, a Monte Carlo simulation was designed to observe the self-assembly of the HIV-1 capsid protein. The simulation allowed a coarse grained model of the capsid protein with
defined interaction sites to move freely in three dimensions using the Metropolis criterion. Observations were made as to which parameters affected the assembly the process. The ways in which the assembly were affected were also noted. It was found that proper dimerization of the capsid protein was necessary in order for the lattice to form properly. It was also found that a strong trimeric interface could be responsible for double-layered assemblies. Further studies may be conducted by further varying of parameters or reworking the dynamics of the simulation. The possible causes of curvature within the assembly still need to be researched further.B.S.
Bachelors
Physics
Sciences