Dissertations / Theses on the topic 'Molecular modeling analysis'
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1
Noel, Adam. "Modeling and analysis of diffusive molecular communication systems." Thesis, University of British Columbia, 2015. http://hdl.handle.net/2429/54906.
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Diffusive molecular communication (MC) is a promising strategy for the transfer of information in synthetic networks at the nanoscale. If such devices could communicate, then it would expand their cumulative capacity and potentially enable applications such as cooperative diagnostics in medicine, bottom-up fabrication in manufacturing, and sensitive environmental monitoring. Diffusion-based MC relies on the random motion of information molecules due to collisions with other molecules. This dissertation presents a novel system model for three-dimensional diffusive MC where molecules can also be carried by steady uniform flow or participate in chemical reactions. The expected channel impulse response due to a point source of molecules is derived and its statistics are studied. The mutual information between consecutive observations at the receiver is also derived. A simulation framework that accommodates the details of the system model is introduced. A joint estimation problem is formulated for the underlying system model parameters. The Cramer-Rao lower bound on the variance of estimation error is derived. Maximum likelihood estimation is considered and shown to be better than the Cramer-Rao lower bound when it is biased. Peak-based estimators are proposed for the low-complexity estimation of any single channel parameter. Optimal and suboptimal receiver design is considered for detecting the transmission of ON/OFF keying impulses. Optimal joint detection provides a bound on detector performance. The weighted sum detector is proposed as a suboptimal alternative that is more physically realizable. The performance of a weighted sum detector can become comparable to that of the optimal detector when the environment has a mechanism to reduce intersymbol interference.
A model for noise sources that continuously release molecules is studied. The time-varying and asymptotic impact of such sources is derived. The model for asymptotic noise is used to approximate the impact of multiuser interference and also the impact of older bits of intersymbol interference.Applied Science, Faculty of
Electrical and Computer Engineering, Department of
Graduate
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Aghaei, Amin. "Symmetry-Adapted Molecular Modeling of Nanostructures and Biomembranes." Research Showcase @ CMU, 2013. http://repository.cmu.edu/dissertations/295.
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Tremendous advances in nanoscience during the past decades have drawn a new horizon for the future of science. Many biological and structural elements such as DNA, bio-membranes, nanotubes, nanowires and thin films have been studied carefully in the past decades. In this work we target to speed up the computational methods by incorporating the structural symmetries that nanostructures have. In particular, we use the Objective Structures (OS) framework to speed up molecular dynamics (MD), lattice dynamics (phonon analysis) and multiscale methods. OS framework is a generalization of the standard idea for crystal lattices of assuming periodicity of atomic positions with a large supercell. OS not only considers the translational periodicity of the structure, but also other symmetries such as rotational and screw symmetries. In addition to the computational efficiency afforded by Objective Structures, OS provides us with more flexibility in the shape of the unit cell and the form of the external deformation and loading, comparing to using the translational periodicity. This is because the deformation and loading should be consistent in all cells and not all deformations keep the periodicity of the structures. For instance, bending and twisting cannot be modeled with methods using the structure's periodicity. Using OS framework we then carefully studied carbon nanotubes under non-equilibrium deformations. We also studied the failure mechanism of pristine and twisted nanotubes under tensile loading. We found a range of failure mechanisms, including the formation of Stone-Wales defects, the opening of voids, and the motion of atoms out of the cross-section. We also used the OS framework to make concrete analogies between crystalline phonons and normal modes of vibration in non-crystalline but highly symmetric nanostructures.
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Peacock, Darren. "Parallelized multigrid applied to modeling molecular electronics." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=101160.
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This thesis begins with a review on the topic of molecular electronics. The purpose of this review is to motivate the need for good theory to understand and predict molecular electronics behaviour. At present the most promising theoretical formalism for dealing with this problem is a combination of density functional theory and nonequilibrium Green's functions (NEGF-DFT). This formalism is especially attractive because it is an ab-initio technique, meaning that it is completely from first principles and does not require any empirical parameters. An implementation of this formalism has been developed by the research group of Hong Guo and is presented and explained here. A few other implementations which are similar but differ in some ways are also discussed briefly to highlight their various advantages and disadvantages.One of the difficulties of ab-initio calculations is that they can be extremely costly in terms of the computing time and memory that they require. For this reason, in addition to using appropriate approximations, sophisticated numerical analysis tech niques need to be used. One of the bottlenecks in the NEGF-DFT method is solving the Poisson equation on a large real space grid. For studying systems incorporating a gate voltage it is required to be able to solve this problem with nonperiodic boundary conditions. In order to do this a technique called multigrid is used. This thesis examines the multigrid technique and develops an efficient implementation for the purpose of use in the NEGF-DFT formalism. For large systems, where it is necessary to use especially large real space grids, it is desirable to run simulations on parallel computing clusters to handle the memory requirements and make the code run faster. For this reason a parallel implementation of multigrid is developed and tested for performance. The multigrid tool is incorporated into the NEGF-DFT formalism and tested to ensure that it is properly implemented. A few calculations are made on a benzenedithiol system with gold leads to show the effect of an applied gate voltage.
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Fang, Yu-Hua. "Quantification of Pharmacokinetics in Small Animals with Molecular Imaging and Compartment Modeling Analysis." Cleveland, Ohio : Case Western Reserve University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=case1238635584.
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Thesis (Ph.D.)--Case Western Reserve University, 2009Department of Biomedical Engineering Abstract Title from OhioLINK abstract screen (viewed on 10 April 2009) Available online via the OhioLINK ETD Center
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Chen, Lulu. "Mathematical Modeling and Deconvolution for Molecular Characterization of Tissue Heterogeneity." Diss., Virginia Tech, 2020. http://hdl.handle.net/10919/96553.
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Tissue heterogeneity, arising from intermingled cellular or tissue subtypes, significantly obscures the analyses of molecular expression data derived from complex tissues. Existing computational methods performing data deconvolution from mixed subtype signals almost exclusively rely on supervising information, requiring subtype-specific markers, the number of subtypes, or subtype compositions in individual samples. We develop a fully unsupervised deconvolution method to dissect complex tissues into molecularly distinctive tissue or cell subtypes directly from mixture expression profiles. We implement an R package, deconvolution by Convex Analysis of Mixtures (debCAM) that can automatically detect tissue or cell-specific markers, determine the number of constituent sub-types, calculate subtype proportions in individual samples, and estimate tissue/cell-specific expression profiles. We demonstrate the performance and biomedical utility of debCAM on gene expression, methylation, and proteomics data. With enhanced data preprocessing and prior knowledge incorporation, debCAM software tool will allow biologists to perform a deep and unbiased characterization of tissue remodeling in many biomedical contexts.
Purified expression profiles from physical experiments provide both ground truth and a priori information that can be used to validate unsupervised deconvolution results or improve supervision for various deconvolution methods. Detecting tissue or cell-specific expressed markers from purified expression profiles plays a critical role in molecularly characterizing and determining tissue or cell subtypes. Unfortunately, classic differential analysis assumes a convenient test statistic and associated null distribution that is inconsistent with the definition of markers and thus results in a high false positive rate or lower detection power. We describe a statistically-principled marker detection method, One Versus Everyone Subtype Exclusively-expressed Genes (OVESEG) test, that estimates a mixture null distribution model by applying novel permutation schemes. Validated with realistic synthetic data sets on both type 1 error and detection power, OVESEG-test applied to benchmark gene expression data sets detects many known and de novo subtype-specific expressed markers. Subsequent supervised deconvolution results, obtained using markers detected by the OVESEG-test, showed superior performance when compared with popular peer methods.
While the current debCAM approach can dissect mixed signals from multiple samples into the 'averaged' expression profiles of subtypes, many subsequent molecular analyses of complex tissues require sample-specific deconvolution where each sample is a mixture of 'individualized' subtype expression profiles. The between-sample variation embedded in sample-specific subtype signals provides critical information for detecting subtype-specific molecular networks and uncovering hidden crosstalk. However, sample-specific deconvolution is an underdetermined and challenging problem because there are more variables than observations. We propose and develop debCAM2.0 to estimate sample-specific subtype signals by nuclear norm regularization, where the hyperparameter value is determined by random entry exclusion based cross-validation scheme. We also derive an efficient optimization approach based on ADMM to enable debCAM2.0 application in large-scale biological data analyses. Experimental results on realistic simulation data sets show that debCAM2.0 can successfully recover subtype-specific correlation networks that is unobtainable otherwise using existing deconvolution methods.Doctor of Philosophy
Tissue samples are essentially mixtures of tissue or cellular subtypes where the proportions of individual subtypes vary across different tissue samples. Data deconvolution aims to dissect tissue heterogeneity into biologically important subtypes, their proportions, and their marker genes. The physical solution to mitigate tissue heterogeneity is to isolate pure tissue components prior to molecular profiling. However, these experimental methods are time-consuming, expensive and may alter the expression values during isolation. Existing literature primarily focuses on supervised deconvolution methods which require a priori information. This approach has an inherent problem as it relies on the quality and accuracy of the a priori information. In this dissertation, we propose and develop a fully unsupervised deconvolution method - deconvolution by Convex Analysis of Mixtures (debCAM) that can estimate the mixing proportions and 'averaged' expression profiles of individual subtypes present in heterogeneous tissue samples. Furthermore, we also propose and develop debCAM2.0 that can estimate 'individualized' expression profiles of participating subtypes in complex tissue samples. Subtype-specific expressed markers, or marker genes (MGs), serves as critical a priori information for supervised deconvolution. MGs are exclusively and consistently expressed in a particular tissue or cell subtype while detecting such unique MGs involving many subtypes constitutes a challenging task. We propose and develop a statistically-principled method - One Versus Everyone Subtype Exclusively-expressed Genes (OVESEG-test) for robust detection of MGs from purified profiles of many subtypes.
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Saraf, Sanjeev R. "Molecular characterization of energetic materials." Texas A&M University, 2003. http://hdl.handle.net/1969.1/331.
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Assessing hazards due to energetic or reactive chemicals is a challenging and complicated task and has received considerable attention from industry and regulatory bodies. Thermal analysis techniques, such as Differential Scanning Calorimeter (DSC), are commonly employed to evaluate reactivity hazards. A simple classification based on energy of reaction (-H), a thermodynamic parameter, and onset temperature (To), a kinetic parameter, is proposed with the aim of recognizing more hazardous compositions. The utility of other DSC parameters in predicting explosive properties is discussed.
Calorimetric measurements to determine reactivity can be resource consuming, so computational methods to predict reactivity hazards present an attractive option. Molecular modeling techniques were employed to gain information at the molecular scale to predict calorimetric data. Molecular descriptors, calculated at density functional level of theory, were correlated with DSC data for mono nitro compounds applying Quantitative Structure Property Relationships (QSPR) and yielded reasonable predictions. Such correlations can be incorporated into a software program for apriori prediction of potential reactivity hazards. Estimations of potential hazards can greatly help to focus attention on more hazardous substances, such as hydroxylamine (HA), which was involved in two major industrial incidents in the past four years. A detailed discussion of HA investigation is presented.
7
Robertson, Scott C. "Mechanisms of protein kinase activation determined by molecular modeling and mutational analysis /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 1999. http://wwwlib.umi.com/cr/ucsd/fullcit?p9938596.
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Sprague, Robin M. "Molecular modeling of DNA with minor groove binding agents and intercalators." Scholarly Commons, 2000. https://scholarlycommons.pacific.edu/uop_etds/539.
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The molecular modeling of several drugs in complexes with deoxyribonucleic acid (DNA) was undet1aken. Selected bis-lexitropsins, based upon NMR and modeling studies of bis-distamycin A, were modeled with an oligonucleotide d(CGAACA TGTTCG)2 using MidasPlus and AMBER 4.0. Intercalators ethidium, ellipticinc. mitoxantrone, and bisantrene were modeled with an oligonucleotide d(CGCG)~ using SpartanPlus and DOCK 4.0. The binding site was prepared from an x-ray study of this oligonucleotide interacting with ditercalinium, a bis-intercalator. The purpost: of this study was to estimate the conformation and orientation of the molecules in tht:ir rt:spcctive binding sites. The mndding study of the bis-lexitropsins showed good agreement with previous modeling studies on distamycin and would be further enhanced by acquisition and interpretation ofNOESY NMR data. The computer modeling study shows that one of the bis-lexitropsins (pyrrole-pyrrole-imidazole, PPI) forms several hydrogen bonds between subunits, which may make it less effective for binding DNA. The other bis-lexitropsin (pyrrole-imidazole-pyrrole, PIP) also forms some interactions between dimers, but is mainly occupied with binding to the DNA and therefore has a more favorable interaction energy for binding to the chosen sequence. The intercalators were similarly agreeable with previous models. Bisantrene has the most favorable interaction energy. It threads its sidechain through the DNA so that while the planar aromatic ring system stacks between base pairs, there is one sidechain in the major groove and one in the minor groove. These extra interactions between the drug and DNA help the interaction to be more favorable.
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Foster, Michael Scott. "Design, synthesis, kinetic analysis, molecular modeling, and pharmacological evaluation of novel inhibitors of peptide amidation." Diss., Atlanta, Ga. : Georgia Institute of Technology, 2008. http://hdl.handle.net/1853/31816.
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Thesis (Ph.D)--Chemistry and Biochemistry, Georgia Institute of Technology, 2009.Committee Chair: Dr. Sheldon W. May; Committee Member: Dr. James C. Powers; Committee Member: Dr. Nicholas Hud; Committee Member: Dr. Niren Murthy; Committee Member: Dr. Stanley H. Pollock. Part of the SMARTech Electronic Thesis and Dissertation Collection.
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Wu, Tzong-Ming. "X-ray analysis and molecular modeling of the structure of aromatic polyimide fibers." Case Western Reserve University School of Graduate Studies / OhioLINK, 1995. http://rave.ohiolink.edu/etdc/view?acc_num=case1062601845.
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Pavan, Giovanni Maria. "Energetic and structural analysis of organic and inorganic systems- the molecular modeling potentiality." Doctoral thesis, Università degli studi di Trieste, 2010. http://hdl.handle.net/10077/3444.
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2008/2009The notable progresses achieved in the medical biotechnology research allowed to identify the common genetic origin of many different pathologies. Genes that, for unknown reasons, mutate during the lifetime of the patient synthesize proteins and receptors that lose the control by grow factors. These aberrant proteins are consequently always active and give rise to a series of cascade signals that result in an uncontrolled proliferation of tumor cells. In this framework, the use of small inhibitor molecules to deactivate these proteins, and consequently to block the diseases, constitutes a revolutionary concept that is the base of the “target therapy”. However, during the treatment, patients develop almost unavoidably resistance toward these kind of drugs that is caused by mutations that interest the amino acidic chains of determined tyrosine kinases (i.e. KIT, PDGFRα, etc.). In this thesis we used molecular modelling techniques to gain an insight in the binding between proteins and inhibitors. In particular, we were able to obtain unique information about the interactions that stabilize the complexation, and consequently about the destabilizing effect induced by mutations in the protein and receptor structures. Our data show that different drugs penetrate differently inside the binding site of kinases during the inhibition. Consequently, the efficiency of each inhibitor molecule is strongly dependent on the situation (mutations) presented by each patient. It becomes thus necessary to create a benchmark of responses related to all the most common mutations treated with different drugs. In this direction, molecular simulation can really support clinical scientists in the comprehension of drug resistance phenomena – a virtual microscope, able to provide unique details to cancer research.
I notevoli progressi compiuti dalla ricerca nelle biotecnologie mediche ha permesso di identificare la comune origine genetica di diverse patologie. Geni che, per cause ancora sconosciute, mutano durante la vita del paziente, sintetizzano proteine e recettori che perdono il controllo da parte dei fattori di crescita. Queste proteine aberranti sono di conseguenza sempre attive e generano una serie di segnali “a cascata” che risultano in una proliferazione incontrollata delle cellule tumorali. In questo ambito, l’uso di piccole molecole inibitrici per deattivare queste proteine, bloccando di conseguenza la progressione delle malattie, costituisce il concetto rivoluzionario che sta alla base della terapia a “bersaglio molecolare” (target therapy). Durante il trattamento tuttavia i pazienti sviluppano quasi inevitabilmente una sorta di resistenza nei confronti dei questo tipo di farmaci che è causato dalla comparsa di mutazioni che interessano la catena aminoacidica di determinate chinasi (KIT, PDGFRα, ecc.). In questa tesi sono state utilizzate tecniche di modellistica molecolare per ottenere un’analisi dettagliata del binding tra proteine e inibitori. In particolare, è stato possibile ottenere importanti informazioni sulle interazioni che stabilizzano la complessazione, e di conseguenza sull’effetto destabilizzante generato da mutazioni che compaiono sulla struttura di proteine e recettori. I nostri risultati mostrano che farmaci diversi penetrano differentemente all’interno del sito di binding delle chinasi durante l’inibizione. L’efficienza di ciascun inibitore risulta quindi essere fortemente dipendente dalla situazione (mutazioni) del singolo paziente. Diviene dunque necessaria la creazione di un benchmark contenente i responsi di tutte le più comuni mutazioni trattate con diversi farmaci. In questa direzione, la simulazione molecolare può fornire un supporto reale alla clinica nella comprensione dei fenomeni di resistenza ai farmaci: un microscopio virtuale, capace di fornire dettagli unici alla ricerca sul cancro.
XXII Ciclo
1981
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Armstrong, Kathryn Anne. "Computational structure-based modeling and analysis with application to rational and evolutionary molecular engineering." Thesis, Massachusetts Institute of Technology, 2007. http://hdl.handle.net/1721.1/39844.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2007.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Includes bibliographical references (leaves 112-127).
The design and development of new proteins and small molecules has considerable practical application in medicine, industry, and basic science. Frequently, progress in this area is made by altering an existing small molecule or protein for new function. This thesis presents methods for the analysis and design of rationally and evolutionarily designed molecules and focuses on applying these methods to make protein and small molecule changes more strategically. First, electrostatic analysis of a series of small molecule neuraminidase inhibitors was used to demonstrate that charge optimization improves the electrostatic component of the binding free energy, despite changes in binding mode and discrete chemical constraints. Additionally, chemical changes suggested by charge optimization frequently corresponded to tighter-binding inhibitors, indicating that this technique would be useful for the design of future inhibitors. Second, computational sequence and structure analysis were used to study the PDZ3-CRIPT binding interaction and a method for sequence analysis was developed to locate residues important for binding specificity. Third, computational analysis of the horseradish peroxidase active site suggested five positions as candidates for mutation, and further studies of new mutant enzymes let to ideas for the improvement of computational enzyme design procedures. Finally, both computational protein design techniques and a model of the evolutionary process were used to study the efficiency of evolution as a tool for creating new proteins in the laboratory. We identified sequences that serve as better evolutionary starting points that others and provide a general framework for considering the impact of protein structure on the allowed sequence space and therefore on the challenges that each protein presents to evolutionary protein engineering procedures.
by Kathryn Anne Armstrong.
Ph.D.
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Venkata, Swamy Sampath Kumar. "Modeling of Nanocomposites Reinforced With Carbon Nanoplatelets Using Molecular Dynamics and Finite Element Analysis." University of Cincinnati / OhioLINK, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1122555750.
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Allen, William Joseph. "Practical Applications of Molecular Modeling Pertaining to Oxidative Damage and Disease." Diss., Virginia Tech, 2011. http://hdl.handle.net/10919/78000.
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Molecular modeling is a term referring to the study of proteins, nucleic acids, lipids, and other bio- or macro- or small molecules at the atomistic level using a combination of computational methods, physico-chemical principles, and mathematical functions. It can be generally sub-divided into two areas: molecular mechanics, which is the treatment of atoms and bonds as Newtonian particles and springs, and quantum mechanics, which models electronic behaviors using the Schrödinger equation and wavefunctions. Each technique is a powerful tool that, when used alone or in combination with wet lab experiments, can yield useful results, the products of which have broad applications in studying human disease models, oxidative damage, and other biomolecular processes that are otherwise not easily observed by experiment alone. Within this document, we study seven different such systems. This includes the mode of inhibitor binding to the enzyme monoamine oxidase B, the active site mechanism of that same enzyme, the dynamics of the unstructured p53 C-terminal domain in complex with globular, structured proteins, the process of the viral protein B2 unbinding from double-stranded RNA, and a focus on the dynamics of a variable loop in the antigenic peanut protein Ara h 2. In addition to those conventional molecular modeling studies, several of which were done in tandem with wet lab experiment, we also discuss the validation of charges and charge group parameters for small molecules used in molecular mechanics, and the development of software for the analysis of lipid bilayer systems in molecular mechanics simulations. As computational resources continue to evolve, and as more structural information becomes available, these methods are becoming an integral part of the study of biomolecules in the context of disease.Ph. D.
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Cocca, Stephanie M. "Phylogenetic analysis, modeling and experimental studies of the Saccharomyces cerevisiae palmitoylated protein kinase gene, ENV7." Thesis, California State University, Long Beach, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=1527907.
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Env7 is a vacuole membrane-localized protein kinase that is orthologous to the human serine/threonine protein kinase, STK16. It is evolutionarily well-conserved throughout Eukarya, and it has one ortholog in Bacteria. Phylogenetic analyses of sequences homologous to Env7 revealed clades that are inconsistent with established eukaryotic phylogeny, suggesting that both horizontal and vertical gene transmission are responsible for their conservation. Conserved amino acid residues and motifs that are potentially important to Env7's catalytic activity, localization, and interactions with other proteins were also identified and assessed. Additionally, one such conserved motif—the glycine-rich loop—was mutated in an effort to affect ATP binding in Env7. The phenotype resulting from this mutation was a slightly increased number of mutant cells exhibiting multi-lobed vacuoles under normal conditions.
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Sprague, Robin M. "Molecular modeling of DNA with minor groove binding agents and intercalators : a thesis." Scholarly Commons, 2001. https://scholarlycommons.pacific.edu/uop_etds/539.
Full textAbstract:
The molecular modeling of several drugs in complexes with deoxyribonucleic acid (DNA) was undet1aken. Selected bis-lexitropsins, based upon NMR and modeling studies of bis-distamycin A, were modeled with an oligonucleotide d(CGAACA TGTTCG)2 using MidasPlus and AMBER 4.0. Intercalators ethidium, ellipticinc. mitoxantrone, and bisantrene were modeled with an oligonucleotide d(CGCG)~ using SpartanPlus and DOCK 4.0. The binding site was prepared from an x-ray study of this oligonucleotide interacting with ditercalinium, a bis-intercalator. The purpost: of this study was to estimate the conformation and orientation of the molecules in tht:ir rt:spcctive binding sites. The mndding study of the bis-lexitropsins showed good agreement with previous modeling studies on distamycin and would be further enhanced by acquisition and interpretation ofNOESY NMR data. The computer modeling study shows that one of the bis-lexitropsins (pyrrole-pyrrole-imidazole, PPI) forms several hydrogen bonds between subunits, which may make it less effective for binding DNA. The other bis-lexitropsin (pyrrole-imidazole-pyrrole, PIP) also forms some interactions between dimers, but is mainly occupied with binding to the DNA and therefore has a more favorable interaction energy for binding to the chosen sequence. The intercalators were similarly agreeable with previous models. Bisantrene has the most favorable interaction energy. It threads its sidechain through the DNA so that while the planar aromatic ring system stacks between base pairs, there is one sidechain in the major groove and one in the minor groove. These extra interactions between the drug and DNA help the interaction to be more favorable.
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Mei, Han. "Homology modeling of aryl hydrocarbon receptor and its ligand-binding properties investigated by molecular dynamics simulation." HKBU Institutional Repository, 2011. http://repository.hkbu.edu.hk/etd_ra/1289.
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Ozer, Gungor. "Understanding protein structure and dynamics: from comparative modeling point of view to dynamical perspectives." Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/39577.
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In this thesis, we have advanced a set of distinct bioinformatic and computational tools to address the structure and function of proteins. Using data mining of the protein data bank (PDB), we have collected statistics connecting the propensity between the protein sequence and the secondary structure. This new tool has enabled us to evaluate new structures as well as a family of structures. A comparison of the wild type staphylococcal nuclease to various mutants using the proposed tool has indicated long-range conformational deviations spatially distant from the mutation point. The energetics of protein unfolding has been studied in terms of the forces observed in molecular dynamics simulations. An adaptive integration of the steered molecular dynamics is proposed to reduce ground state dominance by the rare low energy trajectories on the estimated free energy profile. The proposed adaptive algorithm is utilized to reproduce the potential of mean force of the stretching of decaalanine in vacuum at lower computational cost. It is then used to construct the potential of mean force of this transition in solvent for the first time as to observe the hydration effect on the helix-coil transformation. Adaptive steered molecular dynamics is also implemented to obtain the free energy change during the unfolding of neuropeptide Y and to confirm that the monomeric form of neuropeptide Y adopts halical-hairpin like pancreatic-polypeptide fold.
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Wei, Shuting. "Capturing molecules with templated materials analysis and rational design of molecularly imprinted polymers /." Diss., Atlanta, Ga. : Georgia Institute of Technology, 2007. http://hdl.handle.net/1853/24817.
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Thesis (Ph.D.)--Chemistry and Biochemistry, Georgia Institute of Technology, 2008.Committee Chair: Boris Mizaikoff; Committee Member: Andrew Lyon; Committee Member: Ching-Hua Huang; Committee Member: David Collard; Committee Member: Facundo M. Fernandez.
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Almahmoud, Omar H. M. "Design Optimization of Functionalized Silica-Polymer Nanocomposite through Finite Element and Molecular Dynamics Modeling." Thesis, University of North Texas, 2020. https://digital.library.unt.edu/ark:/67531/metadc1707245/.
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This dissertation focuses on studying membrane air dehumidification for a membrane moisture exchanger in a membrane heat pump system. The study has two parts: an optimization of membrane moisture exchanger for air dehumidification in the macroscale, and diffusion of water vapor in polymer nanocomposites membrane for humid air dehumidification in the nanoscale. In the first part of the research, the mass transport of water vapor molecules through hydrophilic silica nanochannel chains in hydrophobic polyurethane matrix was studied by simulations and experiments for different membrane moisture exchanger design configurations. The mass transport across the polymer nanocomposite membrane occurs with the diffusion of moist air water vapor molecules in the membrane moisture exchanger in a membrane heat pump air conditioning system for air dehumidification purposes. The hydrophobic polyurethane matrix containing the hydrophilic silica nanochannel chains membrane is responsible for transporting water vapor molecules from the feed side to the permeate side of the membrane without allowing air molecules to pass through.In the second part of the research, diffusion analysis of the polymer nanocomposite membrane were performed in the nanoscale for the polymer nanocomposite membrane. The diffusion phenomena through the polymer, the polymer nanocomposite without modifying the silica surfaces, and the polymer nanocomposite with two different silica modified surfaces were studied in order to obtain the highest water vapor removal through the membrane. Different membrane moisture exchanger configurations for optimal water vapor removal were compared to get the desired membrane moisture exchanger design using the finite element method (FEM) with the COMSOL Multiphysics software package. The prediction of mass transport through different membrane configurations can be done by obtaining the mass flux value for each configuration. An experimental setup of one membrane moisture exchanger design was introduced to verify the simulation results. Also, for different membrane structures, permeability was measured according to the ASTM E-96 method. The prediction of water vapor diffusion through the polymer nanocomposite was studied by molecular dynamics simulation with the MAPS 4.3 and LAMMPS software packages. As a new nanocomposite material used in air dehumidification application, water vapor diffusivity through Silica-Polyurethane nanocomposite membranes was measured by the random movement of water vapor molecules through the formed nanochannels in the nanocomposite. For the diffusivity value, the Einstein's relationship was employed for the movement of each single water vapor molecule during the simulation time for all suggested membranes. The results of the proposed research will contribute to enhancing the energy efficiency of air conditioning systems by choosing the membrane moisture exchanger configuration which maximizes water vapor removal while, at the same time, enhancing the silica surfaces with the desired surface modifier that will maximize diffusion through the membrane itself.
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LI, YUCHEN. "MICROALGAE PEPTIDES IN CARDIOVASCULAR DISEASE PREVENTION: STRUCTURE ELUCIDATION,BIOACTIVITY INVESTIGATION,AND IN SILICO MOLECULAR MODELING ANALYSIS." Doctoral thesis, Università degli Studi di Milano, 2021. http://hdl.handle.net/2434/850789.
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Bioactive food-derived peptides have been increasingly studied and the multiple health benefits they provide have been acknowledged. Since the most investigated sources of bioactive peptides are eggs, meat, fish, soybean, wheat, milk, and their derivatives or byproducts. More recently, some attention is being paid to microalgae, a promising unconventional protein source. On this basis, the PhD thesis was focused on the evaluation of the potential of microalgae to generate peptides with cardiovascular-promoting effects, especially hypotensive and antidiabetic activities, by targeting two therapeutic agents – angiotensin I converting enzyme (ACE) and peptidyl-peptidase IV (DPP-IV), respectively. To achieve this objective, multidisciplinary approaches were employed, involving peptidomic techniques to profile the peptide sequences, biochemical tools to analyze the bioactivity, and emerging molecular modelling methods to predict potentially bioactive peptides as well as to explore their possible mechanism of action.
Briefly, the results showed that the protein hydrolysates from spirulina, PBP and chlorella generally presented significant ACE and/or DPP-IV inhibitory activities. By comparison, peptic hydrolysate of spirulina protein showed the best in vitro inhibiting effect on ACE with IC50 value of 0.1 ± 0.04 mg/mL while the tryptic hydrolysate of PBP stands out with the lowest IC50 value of DPP-IV inhibition (0.5 – 1.0 mg/mL). Noticeably, when working on the intestinal Caco-2 cells, all the hydrolysates turned to be less bioactive than in vitro, indicating their susceptibility to metabolic degradation by intestinal cells. This is further in line with the kinetics of DPP-IV inhibition of PBP tryptic hydrolysate working on the intestinal cells, which showed the decreasing trend of its bioactivity after incubation with Caco-2 cells for 3 h. This reflects the issue of peptide bioavailability, which could be stressed in further studies. Moreover, peptides Pep2 (FLKPLGSGK), Pep7 (QIYTMGK), Pep8 (FLFVAEAIYK), and Pep10 (QHAGTKAK) were screened from hydrolysates of chlorella protein by peptidomics combined with docking and MD. The modelling results indicated that they may block the important domain of both ACE and DPP-IV and generate dynamically stable peptide-ACE/DPP-IV complexes. Based on this theoretical evidence, further study will focus on the verification of their actual bioactivity by biochemical approaches.
In conclusion, the bioactivity investigation of microalgae protein hydrolysates provides new evidence that microalgae protein are great sources to produce peptides with health-promoting properties. The exclusive data of peptide characterization makes a foundation to isolate single bioactive peptides as well as offers useful structural and functional implications for food ingredient formulation or pharmacological use.
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Igram, Dale J. "Computational Modeling and Characterization of Amorphous Materials." Ohio University / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1564347980986716.
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Invergo, Brandon M. 1982. "A system-level, molecular evolutionary analysis of mammalian phototransduction." Doctoral thesis, Universitat Pompeu Fabra, 2013. http://hdl.handle.net/10803/145482.
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Phototransduction is the biochemical process by which a light stimulus
is converted to a neuronal signal. The process functions through
complex interactions between many proteins, which work in concert to
tightly control the dynamics of the photoresponse. The primary aim of
this thesis is to describe how the topology and kinetics of these
interactions have given rise to detectable patterns of molecular
evolution. To this end, a secondary aim is to develop a comprehensive
mathematical model of mammalian phototransduction, first through the
improvement of an existing model of the amphibian system and then
through the re-tuning of that model to fit mammalian data. The
results show a striking importance of the signal recovery-related
proteins in shaping the photoresponse. This is reflected in relaxed
evolutionary constraint on those proteins that exert the greatest
dynamic influence. Meanwhile, the proteins most central to the
process, while less important dynamically, are strongly constrained
due to their essentiality in proper signal transduction.La fototransducció és el procés bioquímic pel qual un estímul de llum es converteix en un senyal neuronal. El procés funciona a través d'interaccions complexes entre moltes proteïnes, que funcionen en conjunt per controlar estretament la dinàmica de la fotoresposta. L'objectiu principal d'aquesta tesi és descriure com la topologia i la cinètica d'aquestes interaccions han donat lloc a patrons detectables d'evolució molecular. Amb aquesta finalitat, un objectiu secundari és el desenvolupament d'un model matemàtic integral de la fototransducció en mamífers, primer a través de la millora d'un model existent del sistema d'amfibis i després a través de la refinament d'aquest model per ajustar-lo a les dades de mamífers. Els resultats mostren una importància notable de les proteïnes relacionades amb la recuperació del senyal en la fotoresposta. Això es reflecteix en una relaxació de les constriccions evolutives en les proteïnes que exerceixen la major influència dinàmica. Alhora, les proteïnes més centrals per al procés, tot i essent menys importants dinàmicament, es troben fortament limitades degut a la seva essencialitat en la correcta transducció de senyal.
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Saunders, Christopher T. "Modeling protein evolution : phylogenetic analysis with context-dependent mutation and recapitulation of family divergence via flexible backbone design /." Thesis, Connect to this title online; UW restricted, 2007. http://hdl.handle.net/1773/10254.
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Moore, Zakhia. "Application of X-ray Diffraction Methods and Molecular Mechanics Simulations to Structure Determination and Cotton Fiber Analysis." ScholarWorks@UNO, 2008. http://scholarworks.uno.edu/td/888.
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The results of three very different studies are presented. X-ray diffraction has been utilized for single-crystal structure determinations, fiber diffraction analyses, and in conjunction with molecular modeling of Cellulose IIII. Although each technique is different in its sampling, data acquisition, data treatment, and identification, the common denominator has been the use of x-rays. The single-crystal structure determination of ethylene glycol bis(tropane-3-carboxylate) is presented as an example of the use of modern single-crystal x-ray instrumentation including the use of coupled charged devices (CCDs) as detectors for accurate data collection and rapid elucidation of crystal structures. The structure determination of Cellulose IIII by x-ray diffraction and computer modeling is presented to show how the use of x-rays in weakly diffracting materials can generate a reliable structure and be a key component in model building. Finally, a study is presented in which x-ray fiber diffraction data is utilized to investigate possible correlations between the crystallite orientation, crystallinity, crystallize size and the strength properties of cotton fibers collected from various countries.
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López, Muñoz Laura. "Homology modeling and structural analysis of the antipsychotic drugs receptorome." Doctoral thesis, Universitat Pompeu Fabra, 2010. http://hdl.handle.net/10803/7228.
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Classically it was assumed that the compounds with therapeutic effect exert their action interacting with a single receptor. Nowadays it is widely recognized that the pharmacological effect of most drugs is more complex and involves a set of receptors, some associated to their positive effects and some others to the side effects and toxicity. Antipsychotic drugs are an example of effective compounds characterized by a complex pharmacological profile binding to several receptors (mainly G protein-coupled-receptors, GPCR). In this work we will present a detailed study of known antipsychotic drugs and the receptors potentially involved in their binding profile, in order to understand the molecular mechanisms of the antipsychotic pharmacologic effects.The study started with obtaining homology models for all the receptors putatively involved in the antipsychotic drugs receptorome, suitable for building consistent drug-receptor complexes. These complexes were structurally analyzed and compared using multivariate statistical methods, which in turn allowed the identification of the relationship between the pharmacological properties of the antipsychotic drugs and the structural differences in the receptor targets. The results can be exploited for the design of safer and more effective antipsychotic drugs with an optimum binding profile.
Tradicionalmente se asumía que los fármacos terapéuticamente efectivos actuaban interaccionando con un único receptor. Actualmente está ampliamente reconocido que el efecto farmacológico de la mayoría de los fármacos es más complejo y abarca a un conjunto de receptores, algunos asociados a los efectos terapéuticos y otros a los secundarios y toxicidad. Los fármacos antipsicóticos son un ejemplo de compuestos eficaces que se caracterizan por unirse a varios receptores simultáneamente (principalmente a receptores unidos a proteína G, GPCR). El trabajo de la presente tesis se ha centrado en el estudio de los mecanismos moleculares que determinan el perfil de afinidad de unión por múltiples receptores de los fármacos antipsicóticos.
En primer lugar se construyeron modelos de homología para todos los receptores potencialmente implicados en la actividad farmacológica de dichos fármacos, usando una metodología adecuada para construir complejos fármaco-receptor consistentes. La estructura de estos complejos fue analizada y se llevó a cabo una comparación mediante métodos estadísticos multivariantes, que permitió la identificación de asociaciones entre la actividad farmacológica de los fármacos antipsicóticos y diferencias estructurales de los receptores diana. Los resultados obtenidos tienen interés para ser explotados en el diseño de fármacos antipsicóticos con un perfil farmacológico óptimo, más seguros y eficaces.
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Kimmig, François. "Multi-scale modeling of muscle contraction : From stochastic dynamics of molecular motors to continuum mechanics." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLX071/document.
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L'objectif de cette thèse est la modélisation mathématique des mécanismes de contraction musculaire à l'échelle microscopique dans le but de proposer et d'intégrer ces modèles dans un environnement de simulation cardiaque multi-échelle.Ce travail est réalisé dans le contexte de la médecine numérique, qui propose d'améliorer le traitement des patients par l'utilisation d'outils numériques.La première contribution de cette thèse est une analyse bibliographique des travaux expérimentaux caractérisant l’interaction actine-myosine et ses régulations afin de compiler les informations sous une forme utilisable pour le développement de modèles.Cette étape est une condition préalable essentielle à la modélisation.Nous proposons ensuite une hiérarchie de modèles de contraction musculaire à partir d'un modèle stochastique raffiné existant, mais validé uniquement pour les muscles squelettiques, en appliquant des hypothèses de simplification successives.Les étapes de simplification transforment l'équation différentielle stochastique initiale en une équation aux dérivées partielles avec une description qui fait partie de la famille de modèles dérivée du modèle Huxley'57.Une simplification supplémentaire conduit ensuite à un modèle décrit par un ensemble d'équations différentielles ordinaires.La pertinence des modèles proposés, qui ciblent différentes échelles de temps, est démontrée en les comparant aux données expérimentales obtenues avec des muscles cardiaques, et leur domaine de validité est étudié.Pour intégrer ces descriptions dans un environnement de simulation cardiaque, nous avons étendu ces modèles afin de prendre en compte les mécanismes de régulation de la force qui se produisent in vivo.Cela conduit à de nouvelles équations aux dérivées partielles.Ensuite, nous lions les modèles de contraction microscopiques à un modèle d’organe macroscopique.Nous suivons pour cela une approche fondée sur les principes thermodynamiques pour traiter la nature multi-échelle en temps et en espace du tissu musculaire aux niveaux continu et discret.La validité de cet environnement de simulation est démontrée en présentant sa capacité à reproduire le comportement du coeur et en particulier les caractéristiques essentielles de l'effet Frank-StarlingThis PhD thesis deals with the mathematical description of the micro-scale muscle contraction mechanisms with the aim of proposing and integrating our models into a multiscale heart simulation framework.This research effort is made in the context of digital medicine, which proposes to improve the treatment of patients with the use of numerical tools.The first contribution of this thesis is a literature review of the experimental works characterizing the actin-myosin interaction and its regulations to compile information in a useable form for the development of models.This stage is an essential prerequisite to modeling.We then propose a hierarchy of muscle contraction models starting from a previously proposed refined stochastic model, which was only validated for skeletal muscles, and applying successive simplification assumptions.The simplification stages transform the initial stochastic differential equation into a partial differential equation with a model that is part of the Huxley'57 model family.A further simplification then leads to a description governed by a set of ordinary differential equations.The relevance of these models, targeting different time scales, is demonstrated by comparing them with experimental data obtained with cardiac muscles and their range of validity is investigated.To integrate these microscopic descriptions into a heart simulation framework, we extend the models to take into account the force regulation mechanisms that take place in vivo, leading to the derivation of new partial differential equations.Then, we link the microscopic contraction models to the macroscopic organ model.We follow for that an approach based on the thermodynamical principles to deal with the multi-scale nature in time and space of the muscle tissue at the continuous and at the discrete levels.The validity of this simulation framework is demonstrated by showing its ability to reproduce the heart behavior and in particular to capture the essential features of the Frank-Starling effect
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Ishaq, Muhammad. "X-ray analysis and molecular modeling of the structure of wholly aromatic copolyesters with thiophenyl or oxyphenyl side groups." Case Western Reserve University School of Graduate Studies / OhioLINK, 1995. http://rave.ohiolink.edu/etdc/view?acc_num=case1058446956.
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McGovern, Donna. "Salvinorin A: Fragment Synthesis and Modeling Studies." VCU Scholars Compass, 2009. http://scholarscompass.vcu.edu/etd/1862.
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Salvinorin A is a non-nitrogenous, selective kappa opioid receptor agonist with potent hallucinogenic properties. Because Salvinorin A has no basic nitrogen, it does not readily adhere to the “message-address” concept of selectivity for the opioid receptors. Therefore, a better understanding of how salvinorin A and its analogs interact with the kappa opioid receptor may shed some light on how salvinorin A obtains its potency and selectivity. The structure-affinity relationships (SAFIR) of salvinorin A and its analogs along with a discussion of the selectivity of the opioid receptors, is presented. A fragment of salvinorin A, methyl-3-acetoxy-4-oxocyclohexanecarboxylate, was synthesized to determine if the B, C and D rings are or are not necessary for binding to the opioid receptors. The fragment was found not to bind to the kappa, delta or mu receptor which reinforces the importance of the B, C and D rings in the binding of salvinorin A to the kappa opioid receptor. Homology models of the kappa, delta and mu opioid receptors were constructed based on inactive bovine rhodopsin, light-activated bovine rhodopsin and the human beta-2 adrenergic receptors. The program MODELLER was also used to construct the kappa opioid receptor. Two comparative molecular field analysis (CoMFA) studies are then presented which compared three different types of alignment methods. The alignment methods employed included a receptor-docked alignment in which the salvinorin A analogs were docked into a model of the kappa opioid receptor using the program GOLD. The docked poses for this alignment were chosen based on their similarity to our postulated model of salvinorin A in the kappa opioid receptor. In our model the furan oxygen forms hydrogen bonds with Q115(2.60) and Y320(7.43), the methoxy oxygen of the C-4 position ester group may form a hydrogen bond with Y312(7.35) and the methyl group of the C-2 position acetoxy moiety forms a hydrophobic interaction with Y313(7.36). These interactions are consistent with mutagenesis studies. The other alignment methods employed were a FlexS alignment and a realignment of the receptor-docked poses using the Fit Atoms function within SYBYL. Only the receptor-docked alignment method resulted in robust and predictive CoMFA models which indicates that the analogs may bind to the kappa opioid receptor in a similar but non-identical way. In addition, information from the CoMFA models based on the receptor-docked alignment led to a postulated binding mode for a set of amine analogs of salvinorin A which were not part of the original data set. Docking studies have the positively charged C-2 position amine group interacting with E209(XL2.49) while the furan oxygen and C-4 position ester group interacts with the same residues as in our model of salvinorin A in the kappa opioid receptor. The studies presented here not only support our postulated model of salvinorin A binding to the kappa opioid receptor but may also explain the trend of the beta epimers of the amine analogs to have a higher affinity than the corresponding alpha epimers. Site-directed mutagenesis studies could provide data to support or refute the postulated models of the amines docked in the kappa opioid receptor presented here.
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Fonseca, James E. "Temporal and Steric Analysis of Ionic Permeation and Binding in Na+,K+-ATPase via Molecular Dynamic Simulations." Ohio University / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1210868607.
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Harman, Michael William. "The Biophysical Mechanisms Of Bacterial And Cellular Invasion." Diss., The University of Arizona, 2015. http://hdl.handle.net/10150/595820.
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Advances in genetics and fluorescent protein chemistry have enabled us to fuse fluorescent probes directly to biomolecules in stably growing organisms; making it easier to image the precise position and movement of cells in three dimensions. Fluorescent stains and dyes can be employed in a similar fashion to visualize nano-scale fluctuations in active cellular structures without fixation. While informative and exciting on a qualitatively level, microscopy truly becomes powerful when we can extract meaningful quantitative information. To accomplish this, custom MATLAB (Mathworks, Natick, MA) image analysis algorithms were developed to specifically measure the biophysical parameters related to pathogenesis and function in microbes and mammalian cells. These parameters can then be exploited in the development of biophysical models to validate current measurements, and make critical predictions about the system's behavior, often addressing quantities inaccessible by experimental methods. The following research chapters of this dissertation thoroughly describe how these techniques were developed and applied to study the biophysical mechanisms of bacterial and cellular invasion.
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Mishra, Dipu Kumar. "Some novel transition metal complexes of polydentate ligands: synthesis, physico-chemical characterization and DNA Interaction study." Thesis, University of North Bengal, 2021. http://ir.nbu.ac.in/handle/123456789/4759.
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Palace-Berl, Fanny. "Planejamento, síntese e avaliação da atividade anti-T. cruzi de derivados furfurilidênicos com estruturas azometínica e oxadiazolínica." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/9/9135/tde-15082012-161332/.
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A busca de alternativas terapêuticas para o tratamento da doença de Chagas é de grande importância, visto que atualmente existem apenas dois fármacos disponíveis, o benznidazol e o nifurtimox. Ambos apresentam efeitos adversos consideráveis, sendo utilizado, no Brasil, apenas o benznidazol. Compostos nitro-heterocíclicos com atividade frente ao Trypanosoma cruzi, agente causal da doença de Chagas, tem apresentado resultados promissores. Assim, este trabalho abrange o planejamento, síntese, identificação, avaliação da atividade anti-T. cruzi de 5-nitro furfurilidênicos (IC50 T. cruzi) e a citotoxicidade destes compostos frente a macrófagos de linhagem J774 (IC50 J774). A nifuroxazida, composto-protótipo, inspirou as modificações moleculares originando duas séries de compostos furfurilidênicos, uma com estrutura azometínica, série I, e outra com estrutura oxadiazolínica, série II. A escolha de substituintes foi baseada no diagrama de Craig, sendo selecionados dez substituintes para cada série. Foi avaliada a atividade dos vinte compostos planejados frente ao T. cruzi, dos quais os mais ativos foram: 4-butil-[N\'- (5-nitrofuran-2-il)metileno]benzidrazida (4g - IC50 T. cruzi = 1,05 µM, DP = 0,07) e 3-Acetil-5-(4-butilfenil)-2-(5-nitrofuran-2-il)-2,3-di-idro-1,3,4-oxadiazol (5g - IC50 T. cruzi = 8,27 µM, DP = 0,42). Comparados com os fármacos de referência, benznidazol (IC50 T. cruzi = 22,69 µM, DP = 1,96) e nifurtimox (IC50 T. cruzi = 3,78 µM, DP = 0,10), o composto 4g demonstrou atividade anti-T. cruzi superior a ambos. Todos os compostos apresentaram atividade maior do que a nifuroxazida (IC50 T. cruzi = 120,46 µM, DP = 4,06). Para os ensaios de citotoxicidade, obteve-se para o composto mais ativo frente ao T. cruzi, 4g, IC50 J774 = 28,05 µM, DP = 1,05, e para o composto 5g, obteve-se IC50 J774 = > 400 µM, o que representa que a concentração máxima avaliada deste composto não afetou as células. Ambos apresentaram boa seletividade ao efetuar a relação entre o IC50 J774 e o IC50 T. cruzi. Adicionalmente, foram realizados cálculos de propriedades físico-químicas das estruturas tridimensionais dos compostos, seguido pela análise exploratória de dados por análise de agrupamentos hierárquicos (hierarchical clusters analysis - HCA) e análise de componentes principais (principal component analysis, PCA), possibilitando a identificação das propriedades que mais influenciam na atividade anti-T. cruzi nas séries dos compostos estudados. Os resultados indicaram uma forte influência das propriedades ClogP e momento dipolo, evidenciando a necessidade de um equilíbrio lipofílico/hidrofílico no planejamento de novas moléculas com ação anti-T. cruzi.The search for alternative therapies for the treatment of Chagas disease presents great importance, since there are only two currently available drugs, nifurtimox and benznidazole. Both have considerable adverse effects and, in Brazil, is used only benznidazole. Nitro-heterocyclic compounds with activity against Trypanosoma cruzi, the causative agent of Chagas disease, has shown promising results. Thus, this work includes the design, synthesis, identification, evaluation of anti-T. cruzi activity of 5-nitro-2- furfuriliden (IC50 T. cruzi) and cytotoxicity of these compounds against J774 macrophages cell line (IC50 J774). The nifuroxazide, as a lead compound, inspired the molecular modification leading to two series of furfuriliden compounds, a azometinic structure, series I, and other with oxadiazolinic structure, series II. The choice of substituents was based on the Craig\'s diagram, and ten substituents were selected for each series. We evaluated the activity of twenty compounds designed against T. cruzi, and the most active compounds were: 4-butyl-[N\'-(5-nitrofuran-2-yl) methylene] benzidrazide (4g - IC50 T. cruzi = 1.05 µM, SD = 0.07) and 3-acetyl-5-(4-butylphenyl)-2 -(5-nitrofuran-2-yl)- 2,3-dihydro, 1,3,4-oxadiazole (5g - IC50 T. cruzi = 8.27 µM, SD = 0.42). Compared to the reference drugs, benznidazole (IC50 T. cruzi = 22.69 µM, SD = 1.96) and nifurtimox (IC50 T. cruzi = 3.78 µM, SD = 0.10), the compound 4g demonstrated anti-T. cruzi activity superior to both drugs. All compounds showed better activity than nifuroxazide (IC50 T. cruzi = 120.46 µM, SD = 4.06). For cytotoxicity assays, was found for the most active compound against T. cruzi, 4g, IC50 J774 = 28.05 µM, SD = 1.05, and for compound 5g was obtained IC50 J774 = >400 µM, that represents the maximum concentration of the compound evaluated which did not affect the cells. Both showed good selectivity in the calculation of the ratio between the IC50 T. cruzi and IC50 J774. Additionally, we performed calculations of the physicochemical properties of three-dimensional structures of the compounds, followed by exploratory data analysis including hierarchical cluster analysis (HCA) and principal component analysis (PCA), which contributed to the identification of properties that influence the activity anti-T. cruzi in the series of compounds studied. The findings indicated a significant influence of ClogP and dipole moment properties, pointing out the need of a lipophilic/hydrophilic balance in the designing of novel anti-T. cruzi molecules.
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Alexopoulos, Eftichia. "Crystallographic and modeling studies of intermolecular interactions of biological interest." Doctoral thesis, [S.l.] : [s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=972659137.
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Guo, Xiangxue. "Biochemical and Bioinformatics Analysis of CVAB C-Terminal Domain." Digital Archive @ GSU, 2006. http://digitalarchive.gsu.edu/biology_diss/3.
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Cytoplasmic membrane proteins CvaB and CvaA and the outer membrane protein TolC form the bacteriocin colicin V (ColV) secretion system in Escherichia coli. CvaB functions as an ATP-binding cassette transporter with nucleotide-binding motifs in the C-terminal domain (CTD). To study the role of CvaB-CTD in the ColV secretion, a truncated construct of this domain was made and over-expressed. Different forms of CvaB-CTD were obtained during purification, and were identified as monomer, dimer, and oligomer on gel filtration. Nucleotide binding was shown critical for the CvaB-CTD dimerization: oligomers could be converted into dimers by nucleotide bindings; the removal of nucleotide from dimers resulted in transient monomers followed by CTD oligomerization and aggregation; no dimer form could be cross-linked from the nucleotide-binding deficient mutant D654H. The spatial proximity of the Walker A site and ABC signature motif in CTD dimer was identified through disulfide cross-linking of mixed CvaB-CTD with mutants A530C and L630C, while mutations did not dimerize individually. Those results indicated that the CvaB-CTD formed a nucleotide-dependent head-to-tail dimer. Molecular basis of differential nucleotide bindings was also studied through bioinformatics prediction and biochemical verification. Through sequence alignment and homology modeling with bound ATP or GTP, it was found that the Ser503 and Gln504 on aromatic stacking region (Y501DSQ-loop) of CvaB-CTD provided two additional hydrogen-bonds to GTP, but not to ATP. Site-directed mutations of the S503A and/or Q504L were designed based on the model. While site-directed mutagenesis studies of Walker A&B sites or the ABC signature motif affected little on the GTP-binding preference, the double mutation (S503A/Q504L) on the Y501DSQ-loop increased both ATP-binding and ATPase activity at low temperatures. The double mutant showed slight decrease of GTP-binding and about 10-fold increase of the ATP/GTP-binding ratio. Similar temperature sensitivity in nucleotide-binding and activity assays were identified in the double mutant at the same time. Mutations on the Y501DSQ-loop did not affect the ColV secretion level in vivo. Together, the Y501DSQ-loop is structurally involved in the differential binding of GTP over ATP.
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Gossett, John Jared. "Analysis of macromolecular structure through experiment and computation." Diss., Georgia Institute of Technology, 2013. http://hdl.handle.net/1853/51925.
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This thesis covers a wide variety of projects within the domain of computational structural biology. Structural biology is concerned with the molecular structure of proteins and nucleic acids, and the relationship between structure and biological function. We used molecular modeling and simulation, a purely computational approach, to study DNA-linked molecular nanowires. We developed a computational tool that allows potential designs to be screened for viability, and then we used molecular dynamics (MD) simulations to test their stability. As an example of using molecular modeling to create experimentally testable hypotheses, we were able to suggest a new design based on pyrrylene vinylene monomers. In another project, we combined experiments and molecular modeling to gain insight into factors that influence the kinetic binding dynamics of fibrin "knob" peptides and complementary "holes." Molecular dynamics simulations provided helpful information about potential peptide structural conformations and intrachain interactions that may influence binding properties. The remaining projects discussed in this thesis all deal with RNA structure. The underlying approach for these studies is a recently developed chemical probing technology called 2'-hydroxyl acylation analyzed by primer extension (SHAPE). One study focuses on ribosomal RNA, specifically the 23S rRNA from T. thermophilus. We used SHAPE experiments to show that Domain III of the T. thermophilus 23S rRNA is an independently folding domain. This first required the development of our own data processing program for generating quantitative and interpretable data from our SHAPE experiments, due to limitations of existing programs and modifications to the experimental protocol. In another study, we used SHAPE chemistry to study the in vitro transcript of the RNA genome of satellite tobacco mosaic virus (STMV). This involved incorporating the SHAPE data into a secondary structure prediction program. The SHAPE-directed secondary structure of the STMV RNA was highly extended and considerably different from that proposed for the RNA in the intact virion. Finally, analyzing SHAPE data requires navigating a complex data processing pipeline. We review some of the various ways of running a SHAPE experiment, and how this affects the approach to data analysis.
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komariza, Seyed Omid. "ANALYSIS AND MODELING OF THE ROLES OF ACTIN-MYOSIN INTERACTIONS IN BLADDER SMOOTH MUSCLE BIOMECHANICS." VCU Scholars Compass, 2014. http://scholarscompass.vcu.edu/etd/3651.
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Muscle mechanical behavior potentially plays an important role in some of the most common bladder disorders. These include overactive bladder, which can involve involuntary contractions during bladder filling, and impaired contractility or underactive bladder, which may involve weak or incomplete contractions during voiding. Actin-myosin cross-bridges in detrusor smooth muscle (DSM) are responsible for contracting and emptying the bladder. The total tension produced by muscle is the sum of its preload and active tensions. Studies suggest that actin-myosin cross-links are involved in adjustable preload stiffness (APS), which is characterized by a preload tension curve that can be shifted along the length axis as a function of strain history and activation history. DSM also exhibits length adaptation in which the active tension curve can exhibit a similar shift. Actin-myosin cross-bridges are also responsible for myogenic contractions in response to quick stretch of DSM strips and spontaneous rhythmic contractions (SRC) that may occur during bladder filling. Studies show that SRC may participate in the mechanical regulation of both APS and length adaptation. However, the mechanical mechanisms by which actin-myosin interactions enable this interrelated combination of behaviors remain to be determined and were the primary focus of this dissertation. The objectives of this study were to: 1) provide evidence to support the hypothesis that a common mechanism is responsible for SRC and myogenic contraction, 2) develop a sensor-based mechanical model to demonstrate that SRC in one cell is sufficient to trigger stretch-induced myogenic contraction in surrounding cells and propagate the contraction, and 3) develop a conceptual model with actin-myosin cross-bridges and cross-links that produces the coupled mechanical behaviors of APS, SRC, and length adaptation in DSM. Improved understanding of bladder biomechanics may enable the identification of specific targets for the development of new treatments for overactive and underactive bladder.
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Kumari, Vandana. "Structure-Based Computer Aided Drug Design and Analysis for Different Disease Targets." The Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1311612599.
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Scotti, Luciana. "Modelagem molecular aplicada à cosmetologia: planejamento de compostos antienvelhecimento." Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/9/9139/tde-16082017-180006/.
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Nesta pesquisa, calculou-se, por meio da modelagem molecular, parâmetros físico-químicos importantes à capacidade anti-radicalar de compostos fenólicos extraídos de plantas da flora nacional, Chimarrhis turbinata e Arrabidaea samydoides. As propriedades eletrônicas também podem ser analisadas por meio de superfícies representadas por legendas de cores no campo 3D. Mapa de potencial eletrostático, distribuição orbitalar de HOMO e de LUMO e densidade de spin foram superfícies avaliadas neste trabalho. Em adição, estudos de QSAR (Quantitative Structure-Activity Relationships), cálculos de descritores moleculares holísticos por meio dos programas DRAGON e VOLSURF, cálculos estatísticos incluindo algoritmo genético e PLS (Partial Least Squares), demonstraram a influência de determinadas características moleculares como fundamentais à atividade biológica. A pesquisa concluiu que o grupo farmacofórico favorável à atividade antioxidante é estrutura que apresenta predominantemente características hidrofílicas, grupos hidroxila como substituintes, características eletrônicas favoráveis à doação de elétron e à estabilização do radical fenóxi formado, além de reduzido comprometimento estérico. Consideramos que os métodos empregados no trabalho podem ser considerados como abordagem inovadora para a Ciência Cosmética, indicando potencial ação antioxidante, que poderá ser utilizada em formulações antienvelhecimento.In this research, the calculated physico-chemical parameters, by molecular modelling, have been reported in the literature for supplying important information about the antiradicalar behavior of phenolic compounds, as the studied herein from Chimarrhis turbinata sp. and Arrabidaea samydoides sp. The electronic properties also can be analyzed by means of surfaces represented by legends of colors in the 3D field. Map of electrostatic potential, HOMO and LUMO distribution orbitalar and spin density have been used in this work. In addition, QSAR studies (Quantitative Structure-Activity Relationships), calculations of holistic molecular descriptors by softwares DRAGON and VOLSURF, statistical analysis including genetic algorithm and PLS (Partial Least Squares), demonstrate the influence of the molecular structure in the biological activity. Therefore, pharmacofor favorable to the antioxidant activity structure that presents predominantly characteristic hydrophilic, groups hydroxyl as substituintes, electronic characteristics favorable to the donation of electron and the stabilization of the radical formed, besides reduced inibition esteric. These recent methods can be considered as an innovative approach for Cosmetic Science toward antioxidant action that could be used in antiaging products.
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Hou, Shurong. "Structural Mechanism of Substrate Specificity In Human Cytidine Deaminase Family APOBEC3s." eScholarship@UMMS, 2020. https://escholarship.umassmed.edu/gsbs_diss/1079.
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APOBEC3s (A3s) are a family of human cytidine deaminases that play important roles in both innate immunity and cancer. A3s protect host cells against retroviruses and retrotransposons by deaminating cytosine to uracil on foreign pathogenic genomes. However, when mis-regulated, A3s can cause heterogeneities in host genome and thus promote cancer and the development of therapeutic resistance. The family consists of seven members with either one (A3A, A3C and A3H) or two zinc-binding domains (A3B, A3D, A3D and A3G). Despite overall similarity, A3 proteins have distinct deamination activity and substrate specificity. Over the past years, several crystal and NMR structures of apo A3s and DNA/RNA-bound A3s have been determined. These structures have suggested the importance of the loops around the active site for nucleotide specificity and binding. However, the structural mechanism underlying A3 activity and substrate specificity requires further examination.
Using a combination of computational molecular modeling and parallel molecular dynamics (pMD) simulations followed by experimental verifications, I investigated the roles of active site residues and surrounding loops in determining the substrate specificity and RNA versus DNA binding among A3s. Starting with A3B, I revealed the structural basis and gatekeeper residue for DNA binding. I also identified a unique auto-inhibited conformation in A3B that restricts access to the active site and may underlie lower catalytic activity compared to the highly similar A3A. Besides, I investigated the structural mechanism of substrate specificity and ssDNA binding conformation in A3s. I found an interdependence between substrate conformation and specificity. Specifically, the linear DNA conformation helps accommodate CC dinucleotide motif while the U-shaped conformation prefers TC. I also identified the molecular mechanisms of substrate sequence specificity at -1’ and -2’ positions. Characterization of substrate binding to A3A revealed that intra-DNA interactions may be responsible for the specificity in A3A. Finally, I investigated the structural mechanism for exclusion of RNA from A3G catalytic activity using similar methods.
Overall, the comprehensive analysis of A3s in this thesis shed light into the structural mechanism of substrate specificity and broaden the understanding of molecular interactions underlying the biological function of these enzymes. These results have implications for designing specific A3 inhibitors as well as base editing systems for gene therapy.
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Sheik-Amamuddy, Olivier. "Structural analysis of proteases from South African HIV-1 (subtype C) patients undergoing Lopinavir treatment, using comparative modeling, ligand-docking and molecular dynamics." Thesis, Rhodes University, 2017. http://hdl.handle.net/10962/4931.
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HIV is regarded as one of the most devastating infectious diseases of the last few decades, and has a high prevalence in South Africa, subtype C being the most common. Palliative measures used to fight HIV involve the use various types of inhibitors, including the use of HIV protease inhibitors. Representatives from this class of inhibitors are gradually losing their efficacy due to development of resistance mutations from HIV-1. In this study, compounds from the South African Natural Compound Database (SANCDB) were screened against HIV-1 protease models generated from protease protein sequences belonging to 11 South African HIV patients before and after treatment with Lopinavir. The effect of Lopinavir on the alteration of drug-binding affinity before and after treatment is investigated by molecular docking of the protease against other FDA-approved drugs and detection of mutation types using the HIVdb tool. A network representation of hydrogen bonding between docked ligands and their receptor proteases has been developed and a profiling method of visualizing receptor-ligand docking energies at the local level is presented. Four potential HIV-1 protease inhibitors were identified from the list of 599 natural compounds on the basis of receptor conformation and binding free energy. Ligand stabilities were monitored by 20ns molecular dynamics runs using the GROMACS software.
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Wang, Qi. "Multiscale Modeling of Mechanisms of Substrate Protein Translocation and Degradation Product Release by the Bacterial ClpP Peptidase." University of Cincinnati / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1581333440993555.
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Sharma, R. "Study of glycosyltransferases and other stress-related proteins encoded in chickpea genome and analysis of their structures and functions using molecular modeling and docking." Thesis(Ph.D.), CSIR-National Chemical Laboratory, Pune, 2014. http://dspace.ncl.res.in:8080/xmlui/handle/20.500.12252/1989.
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Li, Yumeng. "Multiscale Modeling of the Effects of Nanoscale Load Transfer on the Effective Elastic Properties of Carbon Nanotube-Polymer Nanocomposites." Diss., Virginia Tech, 2015. http://hdl.handle.net/10919/51197.
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A multiscale model is proposed to study the influence of interfacial interactions at the nanoscale in carbon nanotube(CNT)-polymer nanocomposites on the macroscale bulk elastic material properties. The efficiency of CNT reinforcement in terms of interfacial load transferring is assessed for the non-functionalized and functionalized interfaces between the CNTs and polymer matrix using force field based molecular dynamic simulations at the nanoscale. Polyethylene (PE) as a thermoplastic material is adopted and studied first because of its simplicity. Characterization of the nanoscale load transfer has been done through the identification of representative nanoscale interface elements for unfunctionalized CNT-PE interface models which are studied parametrically in terms of the length of the PE chains, the number of the PE chains and the "grip" position. Referring to the non-functionalized interface, CNTs interact with surrounding polymer only through weakly nonbonded van der Waals (vdW) forces in our study. Once appropriate values of these parameters are deemed to yield sufficiently converged results, the representative interface elements are subjected to normal and sliding mode simulations in order to obtain the force-separation responses at 100K and 300K for unfunctionalized CNT-PE interfaces. To study the functionalization effects, atomistic interface representative elements for functionalized CNT-PE interface are built based on non-functionalized interface models by grafting functional groups between the PE matrix and the graphene sheet. This introduces covalent bonding forces in addition to the non-bonded vdW forces. A modified consistent covalent force field (CVFF) and adaptive intermolecular reactive empirical bond order (AIREBO) potentials, both of which account for bond breaking, are applied to investigate the interfacial characteristic of functionalized CNT-PE interface in terms of the force-separation responses at 100K in both normal opening and sliding mode separations. In these studies, the focus has been on the influence of the functionalization density on the load transfer at the nanoscale interface.
As an important engineering material, Epon 862/DETDA epoxy polymer,a thermoset plastic, has also been used as the polymer matrix material in order to see the difference in interfacial load transfer between a network structured polymer and the amorphous entangled structure of the PE matrix. As for thermoset epoxy polymer, emphasis has been put on investigating the effects of the crosslink density of the epoxy network on the interfacial load transfer ability for both non-functionalized and functionalized CNT-Epoxy interface at different temperatures(100K and 300K) and on the functionalization effect influenceing the interfacial interactions at the functionalized CNT-Epoxy interface.
Cohesive zone traction-displacement laws are developed based on the force-separation responses obtained from the MD simulations for both non-functionalied and functionalized CNT-PE/epoxy interfaces. Using the cohesive zone laws, the influence of the interface on the effective elastic material properties of the nanocomposites are observed and determined in continuum level models using analytic and computational micromechanics approaches, allowing for the assessment of the improvement in reinforcement efficiency of CNTs due to the functionalization. It is found that the inclusion of the nanoscale interface in place of the perfectly bonded interface results in effective elastic properties which are dependent on the applied strain and temperature in accordance with the interface sensitivity to those effects, and which are significantly diminished from those obtained under the perfect interface assumption for non-functionalized nanocomposites. Better reinforcement efficiency of CNTs are also observed for the nanocomposites with the functionalized interface between CNTs and polymer matrix, which results in large increasing for the effective elastic material properties relative to the non-functionalized nanocomposites with pristine CNTs. Such observations indicates that trough controlling the degree of functionalization, i.e. the number and distribution of covalent bonds between the embedded CNTs and the enveloping polymer, one can tailor to some degree the interfacial load transfer and hence, the effective mechanical properties.
The multiscale model developed in this study bridges the atomistic modeling and micromechanics approaches with cohesive zone models, which demonstrates to deepen the understanding of the nanoscale load transfer mechanism at the interface and its effects on the effective mechanical properties of the nanocomposites. It is anticipated that the results can offer insights about how to engineer the interface and improve the design of nanocomposites.Ph. D.
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Shumbusho, Félicien. "Designing, technical evaluation and profitability estimation of breeding strategies based on molecular information for small ruminant species." Thesis, Toulouse, INPT, 2014. http://www.theses.fr/2014INPT0005/document.
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La sélection génomique (SG) des animaux et des plantes a été rendue possible grâce aux avancées des biotechnologies, notamment des puces à ADN de haute densité et de faible coût. Son efficacité et sa profitabilité a été clairement démontrée chez les bovins laitiers, où elle a été très rapidement mise en pratique. En revanche, son application pour les petits ruminants est encore limitée, et, notamment, n’a pas démarré en France. Ses potentialités sont toutefois à l’étude dans quelques programmes concernant les ovins et caprins laitiers, et les responsables des filières correspondantes désirent connaitre l’efficacité de cet outil dans leur situation. Cependant, la prudence est de règle, compte tenu des différences entre les schémas de sélection des bovins laitiers et des petits ruminants. Cette étude fait partie d’un programme entrepris pour évaluer l’utilisation et la gestion de l’information génomique dans les schémas de sélection ovin et caprin. Au cours de cette thèse ont été examinés (1) l’impact de la SG sur le gain génétique dans des schémas de sélection de petits ruminants, (2) l’efficacité économique de la SG en petits ruminants, en prenant l’exemple d’un programme de sélection ovin-viande; (3) l’importance d’une optimisation de certaines décisions (quantifiées par des variables dans un modèle décrivant les schémas) pour maximiser le progrès génétique et (4) une piste contribuant à l’optimisation de la population de référence. Les modèles utilisés appartiennent au champ des méthodes déterministes et les exemples ont porté sur les schémas de sélection existants (ovins laitiers, ovins viande et caprins laitiers). Les résultats de cette étude suggèrent que la sélection génomique peut être plus rentable que la sélection classique en terme de gain génétique, à condition qu’une population de référence de taille moyenne soit disponible (environ 2000 individus). Ils montrent, en particulier dans les schémas laitiers, que le potentiel de la SG de réduire l’intervalle de génération pourrait fortement augmenter le gain génétique. Dans le schéma ovin allaitant modélisé, combiner l’information génomique et les phénotypes de caractères bouchers donne plus de gain génétique que la sélection classique ou la SG sans phénotype sur les candidats. En termes d’impacts économiques, les résultats du schéma ovin allaitant modélisé montrent que toutes les stratégies de sélection génomiques sont plus onéreuses que la sélection classique. Cependant, les gains marginaux (recettes totales moins coûts variables) de certains scénarii de SG s’avèrent légèrement plus élevés que pour la sélection classique. L’étude montre également, dans tous les schémas et stratégies de sélection, que l’optimisation de l’utilisation de variables de décision pourrait grandement augmenter le gain génétique et l’efficacité économique, par rapport aux situations actuelles. Avec cette étude, on peut conclure que la mise en place de la sélection génomique dans les programmes de sélection des petits ruminants est possible et pourrait être plus bénéfique que la sélection classique dans certains cas. Cependant, il y a plus d’obstacles par rapport aux bovins laitiers, en particulier, la construction d’une population de référence fiable et des coûts élevés de génotypages par rapport à la valeur des candidats à la sélection. Ces obstacles pourraient freiner sa mise en œuvre, voire l’empêcher dans certaines racesImplementing genomic selection (GS) in small ruminant breeding programs is still at the research and development level. This new way of selection in animals and plants was made possible thanks to the development of low costs, high density SNP chips. It proved to be highly beneficial in dairy cattle breeding programs. The French small ruminant industries are strongly interested in evaluating the efficiency of this tool in their situation. However, they are also very cautious given the inherent differences in terms of capacity and functionalities between dairy cattle and small ruminant breeding programs. This study is part of bigger efforts mobilized to evaluate the use and management of genomic information in sheep and goats breeding programs. The PhD work examined (1) the impact of genomic selection on genetic gain of small ruminant breeding programs; (2) the economic efficiency of genomic selection in small ruminant, through an example of a meat sheep breeding program; (3) the benefits of optimizing the use of decision variables on genetic gain; and (4) contributed some ideas on how to optimize the choice of individuals in the reference population. The modeling parts were done by deterministic methods and the examples focused on the existing breeding programs (dairy sheep, meat sheep and dairy goats) with medium to small size breeding units. The results of this study suggest that adopting genomic selection can be more profitable than classic selection in terms of genetic gain, provided that, at least, a medium size reference population is available (around 2,000 individuals). They show, especially in dairy breeds, that the GS potentials of reducing generation interval could greatly increase the genetic gain. In meat sheep breeding program, exploring the possibility of combining genomic information and meat phenotypes gave higher genetic gain than classic or pure genomic selection. In terms of economic impacts, results of the meat sheep breeding program we modeled show that all genomic selection strategies are more expensive than classic selection. However, the contribution margins (total revenues minus total variable costs) of some GS variants were slightly higher than benefits from classic selection. The study also shows, across breeds and selection strategies, that optimizing the use of decision variables could greatly increase the genetic gain and benefits, compared to the current situation. With this thesis we can conclude that adopting genomic selection in small ruminant breeding programs is possible and could be more beneficial than classic selection in some cases. However, there are more obstacles compared to dairy cattle, especially, construction of reliable reference populations and high costs of genotypes relative to the value of selection candidates. These might delay implementation in general or prevent it in some breeds
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Beyerlein, Kenneth Roy. "Simulation and modeling of the powder diffraction pattern from nanoparticles: studying the influence of surface strain." Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/41211.
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Accurate statistical characterization of nanomaterials is crucial for their use in emerging technologies. This work investigates how different structural characteristics of metal nanoparticles influence the line profiles of the corresponding powder diffraction pattern. The effects of crystallite size, shape, lattice dynamics, and surface strain are all systematically studied in terms of their impact on the line profiles.
The studied patterns are simulated from atomistic models of nanoparticles via the Debye function. This approach allows for the existing theories of diffraction to be tested, and extended, in an effort to improve the characterization of small crystallites. It also begins to allow for the incorporation of atomistic simulations into the field of diffraction. Molecular dynamics simulations are shown to be effective in generating realistic structural models and dynamics of an atomic system, and are then used to study the observed features in the powder diffraction pattern.
Furthermore, the characterization of a sample of shape controlled Pt nanoparticles is carried out through the use of a developed Debye function analysis routine in an effort to determine the predominant particle shape. The results of this modeling are shown to be in good agreement with complementary characterization methods, like transmission electron microscopy and cyclic voltammetry.
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MIO, ANDREA. "A multiscale methodology for the preliminary screening of alternative process designs from a sustainability viewpoint adopting molecular and process simulation along with data envelopment analysis." Doctoral thesis, Università degli Studi di Trieste, 2018. http://hdl.handle.net/11368/2919629.
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La ricerca scientifica nell’ambito dell’ingegneria chimica si è focalizzata sia sul perfezionamento delle teorie e delle tecniche utilizzate attualmente, che sullo sviluppo di nuovi strumenti atti a risolvere le problematiche ancora insolute relative alle produzioni di beni e servizi tipici delle industrie chimiche, biochimiche e farmaceutiche.
In questo panorama, gli approcci multiscala si sono rivelati molto utili grazie alla loro peculiarità di coniugare aspetti che spaziano dalla quanto-meccanica tipica della nanoscala, alla meccanica classica dei materiali massivi, comprendendo prospettive molto ampie e adattando ogni teoria alle diverse applicazioni.
Inoltre, il riconoscimento dei concetti legati alla sostenibilità come principi cardine per ottenere uno sviluppo sostenibile ha generato un prolifico incremento della diffusione di metodologie per considerare aspetti sociali e ambientali, a fianco delle tradizionali stime economiche, nel quadro più ampio delle valutazioni degli impianti chimici.
Di conseguenza, questa tesi tratta dello sviluppo di una metodologia multiscala per la stima preliminare di diverse configurazioni impiantistiche, promuovendo l’adozione di strumenti computazionali differenti e comprendendo valutazioni di carattere economico, sociale e ambientale.
Il fine ultimo che tale metodologia si prefigge risiede nella soddisfazione della necessità tipica di qualsiasi impianto di produzione, ovvero nella definizione di una metodologia di valutazione di vari parametri e configurazioni impiantistiche, utilizzando un’ottica sostenibile e fornendo risultati velocemente.
Al lettore verranno fornite le adeguate informazioni sull’argomento in maniera progressiva attraverso i capitoli di questa tesi.
Nel Chapter I saranno descritti il concetto di sostenibilità e di sviluppo sostenibile. Seguirà una trattazione riguardante la loro applicazione nella società odierna da diverse prospettive: a partire da quella più generalista delle istituzioni, fino a quella più particolare dell’industria, per concludere con una parte specifica sull’industria chimica, corredata di esempi di metodologie applicate a processi chimici.
Il Chapter II descriverà i passaggi necessari ad ottenere la valutazione della sostenibilità delle alternative impiantistiche. Dal reperimento delle informazioni necessarie, all’implementazione dei modelli nei simulatori di processo, seguito dal calcolo degli indici rappresentativi dei pilastri della sostenibilità, i cui valori vengono successivamente valutati tramite un algoritmo matematico (DEA) per identificare la configurazione impiantistica ottimale. Infine è necessario analizzare le alternative inefficienti di modo da comprendere su quali variabili si debba intervenire per migliorarne le prestazioni attraverso una retrofit analisi.
Il Chapter III affronterà l’utilizzo di diverse tecniche di simulazione molecolare per la stima del coefficiente di ripartizione ottanolo-acqua (Kow), che è un proprietà fondamentale per il calcolo di alcuni indici utilizzati.
Il lettore troverà alcuni casi di studio descritti nel Chapter IV. Il primo appartiene al ramo della farmaceutica e si occupa della produzione del pioglitazone cloridrato attraverso l’utilizzo di diverse vie di sintesi appartenenti a numerosi brevetti. La seconda applicazione della metodologia riguarda l’industria biochimica e ottimizza le condizioni operative di un reattore utilizzato per la produzione di biodiesel a partire da olio vegetale. L’ultimo caso di studio esplora il mondo dei materiali nanostrutturati, valutando diversi parametri di reazione utilizzati per condurre la sintesi di CdSe quantum dot.
L’ultimo Chapter V conterrà le valutazioni conclusive e le prospettive future.Research activity in chemical engineering is focused on the refinement of theories and techniques employed for the development of new tools aiming at solving issues directly related to the generation of goods and services supplied by chemical, biochemical and pharmaceutical industries. In this context, multiscale approaches revealed to be very useful, since they embrace theories from quantum mechanics at the nanoscale to classical mechanics at the macroscale, contemplating wide perspectives and enabling the adaptation of each theory to an abundance of disparate applications. Furthermore, the acknowledgment of sustainability among the cornerstones of future development led to a copious diffusion of sustainability evaluation methodologies, aiming to account for economic, social and environmental concerns among chemical processes assessments. Therefore, this thesis deals with the development of a multiscale framework for the preliminary screening of chemical process designs, promoting the adoption of various computational tools along with sustainability considerations. The purpose of this methodology resides in the fulfillment of an emblematic need for any production site, i.e. evaluating a production process considering possible modifications from different perspectives in order to identify as fast as possible the most efficient design including economic, social and environmental concerns. The reader will be guided through this topic following the chapters of this dissertation. In Chapter I, the concept of sustainability and sustainable development will be presented, followed by some applications starting from the wider panorama of institutions to the industry perspective, concluding with some relevant examples from chemical process engineering. Chapter II will describe each step to be performed in order to gain the sustainability evaluation of the process alternatives. From retrieving the promising process designs, to implementing each flowsheet in a process simulator, then calculating several indicators based on the sustainability pillars, which is followed by employing a mathematical tool (DEA) in order to select the most efficient designs and finally investigating how to enhance the sub-optimal alternatives through a retrofit analysis. Chapter III will deal with the application of different molecular simulation techniques in order to estimate the octanol-water partition coefficient (Kow), which is an essential parameter for the calculation of several sustainability indicators. Then the reader will encounter the three case studies shown in details in Chapter IV. The first one belongs to the pharmaceutical field and deals with the production of pioglitazone hydrochloride considering different synthesis routes from various patents. The second application regards the biochemical industry, optimizing the operating conditions of a reactor employed for the production of biodiesel from vegetable oil. The last one explores the synthesis of nanomaterials, evaluating several reaction parameters involved in the laboratory production of CdSe quantum dots from a sustainability viewpoint. Some concluding remarks and future perspectives will be included in the final Chapter V.
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Chen, Xi. "Automatic 13C Chemical Shift Reference Correction of Protein NMR Spectral Data Using Data Mining and Bayesian Statistical Modeling." UKnowledge, 2019. https://uknowledge.uky.edu/biochem_etds/40.
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Nuclear magnetic resonance (NMR) is a highly versatile analytical technique for studying molecular configuration, conformation, and dynamics, especially of biomacromolecules such as proteins. However, due to the intrinsic properties of NMR experiments, results from the NMR instruments require a refencing step before the down-the-line analysis. Poor chemical shift referencing, especially for 13C in protein Nuclear Magnetic Resonance (NMR) experiments, fundamentally limits and even prevents effective study of biomacromolecules via NMR. There is no available method that can rereference carbon chemical shifts from protein NMR without secondary experimental information such as structure or resonance assignment.
To solve this problem, we constructed a Bayesian probabilistic framework that circumvents the limitations of previous reference correction methods that required protein resonance assignment and/or three-dimensional protein structure. Our algorithm named Bayesian Model Optimized Reference Correction (BaMORC) can detect and correct 13C chemical shift referencing errors before the protein resonance assignment step of analysis and without a three-dimensional structure. By combining the BaMORC methodology with a new intra-peaklist grouping algorithm, we created a combined method called Unassigned BaMORC that utilizes only unassigned experimental peak lists and the amino acid sequence.
Unassigned BaMORC kept all experimental three-dimensional HN(CO)CACB-type peak lists tested within ± 0.4 ppm of the correct 13C reference value. On a much larger unassigned chemical shift test set, the base method kept 13C chemical shift referencing errors to within ± 0.45 ppm at a 90% confidence interval. With chemical shift assignments, Assigned BaMORC can detect and correct 13C chemical shift referencing errors to within ± 0.22 at a 90% confidence interval. Therefore, Unassigned BaMORC can correct 13C chemical shift referencing errors when it will have the most impact, right before protein resonance assignment and other downstream analyses are started. After assignment, chemical shift reference correction can be further refined with Assigned BaMORC.
To further support a broader usage of these new methods, we also created a software package with web-based interface for the NMR community. This software will allow non-NMR experts to detect and correct 13C referencing errors at critical early data analysis steps, lowering the bar of NMR expertise required for effective protein NMR analysis.
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Kirch, Alexsandro. "Modelagem e caracterização de sistemas nanofluidos através de simulações moleculares em multiescala." Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/43/43134/tde-28092018-152059/.
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As propriedades físicas incomuns exibidas por fluidos confinados em meios porosos desempenham um papel importante em diversos processos químicos, geoquímicos e ambientais. Atualmente, muitos aspectos da estrutura e dinâmica dos fluidos espacialmente confinados ainda são pouco compreendidos. Nesse contexto, fenômenos interfaciais influenciam consideravelmente os processos que ocorrem em meios nanoporosos, podendo resultar em efeitos relevantes para o desenvolvimento dos dispositivos nanofluidicos. Esses sistemas multifásicos e com fenômenos multifísicos podem apresentar propriedades eletrônicos e dinâmicos envolvendo diferentes escalas de tamanho e tempo na interface sólido/fluido. Atualmente, uma única metodologia não é capaz de resolver toda a complexidade encontrada em tais sistemas pelo fato de cada qual estar restrita a uma escala ou demanda computacional específica. Além disso, as metodologias habitualmente aplicadas para investigar as fases bulk através da modelagem computacional, em geral, não são adequadas para acessar sistematicamente os efeitos de superfície que ocorrem na interface sólido/fluido. Os desafios impostos à modelagem molecular pelos sistemas nanofluídicos requerem iniciativas inovadoras (dentre as metodologias disponíveis) para acessar as propriedades de interface. Nessa tese, desenvolvemos e aplicamos novas abordagens computacionais em nível atômico a fim de modelar e caracterizar sistemas nanofluidicos. Nesse contexto, introduzimos um método multinível hierárquico top-down, que combina simulações de dinâmica molecular com cálculos ab initio de transporte eletrônico, para abordar fenômenos de multiescala. O potencial dessa implementação foi demonstrado em um estudo de caso envolvendo o fluxo de água e o transporte de íons através de um nanotubo de carbono tipo (6,6). Mostramos que o traço iônica pode representar uma mudança na condutância elétrica do nanocanal, e levar a uma medida indireta da corrente iônica. Também implementamos uma versão modificada da análise de rede de ligações de hidrogênio baseada em teoria de grafos, a fim de fazer o estudo das propriedades estruturais e dinâmicas em diferentes regiões do poro. Com essa abordagem, nós fomos capazes de explorar sistematicamente os efeitos de interface em fluidos espacialmente confinados. Combinando-se simulações de dinâmica molecular com a análise da rede de ligações de hidrogênio em camadas, nós pudemos avaliar a extensão dos efeitos de superfície nas propriedades dinâmicas e os detalhes da interface calcita/salmoura. Com a abordagem desenvolvida, conseguimos isolar os efeitos específicas dos íons da solução aquosa na rede de ligações de hidrogênio. Mostramos que a camada superficial exibe uma topologia de rede semelhante à observada em água pura, uma vez que a barreira eletrostática e física exibida por essa região, inibe a adsorção de íons na superfície da calcita. Fora dessa faixa, os íons influenciam consideravelmente a rede de ligações de hidrogênio: observamos a formação caminhos geodésicos mais extensos em relação àqueles observados em água pura. Esses ramos, que são formados por ligações de hidrogênio contíguas, podem conectar moléculas de baixa a alta dinâmica. Tal estrutura, pode explicar as propriedades mecânicas adesivas observadas em fluidos altamente confinados. Nossas principais contribuições decorrem na descrição da estrutura do solvente, dos íons da solução aquosa na interface calcita/fluido; e suas indicações físicas, e seu potencial significado nos processos de crescimento e dissolução de cristais. Nossas implementações fornecem contribuições interessantes para a compreensão atual dos processos que ocorrem em meios porosos. Especialmente, podendo contribuir para um desenvolvimento racional de novos dispositivos nanofluidicos.The unusual physical properties exhibit by fluids within nanoscopic porous media play an important role in the plethora of chemical, geochemical and environmental processes. Currently, many aspects of the structure and dynamics of the spatially constrained fluids are still poorly understood. Additionally, the interfacial phenomena considerably influences the processes occurring in nanoporous media, which can have a major effect on nanofluidics devices. These multiphase systems and multi-physics phenomena occurs at solid/solution interfaces, with electronic and dynamic effects taking place across size and time scales. Currently, a single methodology is not capable to disentangle all the complexity find in such systems because it is restricted to a specific scale or computationally demand. In addition, the usual computational modeling methodologies applied to investigate bulk phases, they are, in general, not suitable to systematically access the surface effects occurring at solid/fluid interfaces. The challenges imposed by the nanofludics-based systems within the molecular modeling framework require innovative initiatives (among the available methodologies) to correctly access the interface properties. In this thesis, we develop and apply novel computational approaches to properly design and characterize nanofluidics-based systems at atomic level. In this context, we introduced an hierarchical top-down multilevel method by combining molecular dynamics simulations with first principles electronic transport calculations to address the multiscale phenomena problem. The potential of this implementation was demonstrated in a case study involving the water and ionic (Na, Li, and CL) flow through a (6,6) carbon nanotube. We showed that the ionic trace, observed on the electronic transmittance, it may handle an indirect measurement of the ionic current that is recorded as a sensing output. We implemented also a layered version of hydrogen bond network analysis based on graph theory. With this approach, we were able to properly explore interface effects arising on spatially confined fluids. By combining molecular dynamics simulations with the layered hydrogen bond network analysis, we evaluated the extension of surface effects on the fluids dynamics properties and the interaction details at calcite/brine interface. With the developed approach, we have been able to isolate the specific features of the aqueous solutions ions on the hydrogen bond network. We showed that the surface layer near the calcite/brine interface displays similar network topology as observed in pure water, since the electrostatic and physical barrier displayed by this layer inhibit the adsorption of ions on the calcite surface. Outside that region, these ions affect the hydrogen bond network. We observed a more extended geodesic paths with respect to that observed in pure water. Such hydrogen bond branches may connect low to high dynamics molecules across the pore and hence, it may explain the glue-like mechanical properties observed in confinement environment. Our main contributions in this work relies on describing the structure of solvent and electrolyte aqueous solution at calcite/fluid interface and their physical indications and potential significance on the crystal growth and dissolution processes. Our implementations provide interesting contributions to the current understanding of processes occurring in porous media. Specially, it may contribute on the rational design of novel nanofluidics devices.
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Tsao, Tzu-Hsin B. "From molecular pathways to neural populations: investigations of different levels of networks in the transverse slice respiratory neural circuitry." Diss., Georgia Institute of Technology, 2010. http://hdl.handle.net/1853/37296.
Full textAbstract:
By exploiting the concept of emergent network properties and the hierarchical nature of networks, we have constructed several levels of models facilitating the investigations of issues in the area of respiratory neural control. The first of such models is an intracellular second messenger pathway model, which has been shown to be an important contributor to intracellular calcium metabolism and mediate responses to neuromodulators such as serotonin. At the next level, we have constructed new single neuron models of respiratory-related neurons (e.g. the pre-Btzinger complex neuron and the Hypoglossal motoneuron), where the electrical activities of the neurons are linked to intracellular mechanisms responsible for chemical homeostasis. Beyond the level of individual neurons, we have constructed models of neuron populations where the effects of different component neurons, varying strengths and types of inter-neuron couplings, as well as network topology are investigated.
Our results from these simulation studies at different structural levels are in line with experiment observations. The small-world topology, as observed in previous anatomical studies, has been shown here to support rhythm generation along with a variety of other network-level phenomena. The interactions between different inter-neuron coupling types simultaneously manifesting at time-scales orders of magnitude apart suggest possible explanations for variations in the outputs measured from the XII rootlet in experiments. In addition, we have demonstrated the significance of pacemakers, along with the importance of considering neuromodulations and second-messenger pathways in an attempt to understand important physiological functions such as breathing activities.