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Blazhynska, Marharyta. "Modeling and Standard Binding Free Energy Calculations of Complex Biological Objects". Electronic Thesis or Diss., Université de Lorraine, 2023. http://www.theses.fr/2023LORR0149.
Pełny tekst źródłaDuring my thesis, I focused my research on analyzing the calculations of absolute binding free energy in protein-ligand complexes. I utilized approaches based on molecular dynamics, incorporating restraints such as alchemical and geometrical routes. My work involved studying three distinct protein-ligand complexes, contributing to the evaluation of the BFEE2 software for automating these calculations. Continuing my investigations, I applied this methodology to protein-protein interactions, which involve more complex recognition and association phenomena. I examined a specific example: a dimer of porcine insulin, where dimerization was induced by hydrophobic interactions at the interface of the monomers. Subsequently, I compared the results of calculated estimates of binding free energy with the corresponding experimental data. To deepen my understanding of binding free energy calculations in protein-ligand and protein-protein complexes, I conducted methodological research. I evaluated the robustness of the geometrical route compared to a simplified version, where additional degrees of freedom remained unrestrained during the physical separation of the partners. After demonstrating the accuracy of the geometrical route, I expanded its application to predict and evaluate the binding affinities of SARS-CoV-2 variants in interaction with a human receptor and antibodies. Additionally, I explored strategies to accelerate the calculations using the MTS option available in the Colvars module, with or without the HMR trick. By adjusting the parameters of Colvars, I achieved an almost threefold acceleration of the calculations without compromising the accuracy of the binding free energy calculations
Ranganathan, Anirudh. "Protein – Ligand Binding: Estimation of Binding Free Energies". Thesis, KTH, Skolan för kemivetenskap (CHE), 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-147527.
Pełny tekst źródłaRocklin, Gabriel Jacob. "Predicting charged protein-ligand binding affinities using free energy calculations". Thesis, University of California, San Francisco, 2013. http://pqdtopen.proquest.com/#viewpdf?dispub=3587895.
Pełny tekst źródłaPredicting protein-ligand binding free energy from physical principles is a grand challenge in biophysics, with particular importance for drug discovery. Free energy calculations compute binding affinities by using classical mechanics to model the protein and ligand at atomic resolution, and using statistical mechanics to analyze simulations of these models. The binding affinities computed from these simulations are fully rigorous and thermodynamically correct for the model (with adequate sampling), and will agree with experimentally measured binding affinities if the model is accurate. Because free energy calculations capture the full statistical complexity of binding for flexible molecules at ambient temperature, they offer the greatest potential for quantitative accuracy of any physical method for predicting binding.
Here, I (& coauthors) present several studies relating to using free energy calculations to predict protein-ligand binding affinities for charged compounds. First, we introduce the Separated Topologies method, an approach for using free energy calculations to predict relative binding affinities of unrelated ligands. This method is useful for studying charged compounds because charged compounds are very difficult to study using absolute binding calculations, increasing the importance of relative binding calculations. Second, we use free energy calculations to predict absolute binding affinities for charged molecules to a simplified protein binding site, which is specially designed for studying charged interactions. These predictions are compared to new experimental affinity measurements and new high-resolution structures of the protein-ligand complexes. We find that all affinities are predicted to be too strong, and that this error is directly correlated with the polarity of each ligand. By uniformly weakening the strength of electrostatic interactions, we are more successful at predicting binding affinity. Third, we design and validate an analytical correction scheme to correct binding free energy calculations of ions for artifacts caused by the periodic boundary conditions employed in simulations. Fourth, we examine the sensitivity of binding affinities from free energy calculations to the force field parameters used in the simulations. This provides insight into the strength of electrostatic interactions in protein simulations, complementing our previous work comparing simulation results to experiments. Finally, we discuss potential future directions of this work.
Cabedo, Martinez Ana. "Computing free energy, binding and competition within Fragment Based Drug Discovery". Thesis, University of Southampton, 2016. https://eprints.soton.ac.uk/403850/.
Pełny tekst źródłaLee, Lee-Peng 1969. "Optimization of electrostatic binding free energy : application to barnase and barstar". Thesis, Massachusetts Institute of Technology, 1999. http://hdl.handle.net/1721.1/85331.
Pełny tekst źródłaWall, Ian. "New simulation methods for the prediction of binding free energies". Thesis, University of Southampton, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.313217.
Pełny tekst źródłaDurmaz, Vedat [Verfasser]. "Atomistic Binding Free Energy Estimations for Biological Host–Guest Systems / Vedat Durmaz". Berlin : Freie Universität Berlin, 2016. http://d-nb.info/1122111215/34.
Pełny tekst źródłaHe, Peng. "FREE ENERGY SIMULATIONS AND STRUCTURAL STUDIES OF PROTEIN-LIGAND BINDING AND ALLOSTERY". Diss., Temple University Libraries, 2018. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/531465.
Pełny tekst źródłaPh.D.
Protein-ligand binding and protein allostery play a crucial role in cell signaling, cell regulation, and modern drug discovery. In recent years, experimental studies of protein structures including crystallography, NMR, and Cryo-EM are widely used to investigate the functional and inhibitory properties of a protein. On the one hand, structural classification and feature identification of the structures of protein kinases, HIV proteins, and other extensively studied proteins would have an increasingly important role in depicting the general figures of the conformational landscape of those proteins. On the other hand, free energy calculations which include the conformational and binding free energy calculation, which provides the thermodynamics basis of protein allostery and inhibitor binding, have proven its ability to guide new inhibitor discovery and protein functional studies. In this dissertation, I have used multiple different analysis and free energy methods to understand the significance of the conformational and binding free energy landscapes of protein kinases and other disease-related proteins and developed a novel alchemical-based free energy method, restrain free energy release (R-FEP-R) to overcome the difficulties in choosing appropriate collective variables and pathways in conformational free energy methods like umbrella sampling and metadynamics.
Temple University--Theses
Bertazzo, Martina <1990>. "Dynamic Docking, Path Analysis and Free Energy Computation in Protein-Ligand Binding". Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2020. http://amsdottorato.unibo.it/9290/1/TESI.pdf.
Pełny tekst źródłaAlsayed, Adnan. "A government and binding approach to restrictive relatives, with particular reference to restrictive relatives in standard Arabic". Thesis, University of Essex, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.243350.
Pełny tekst źródłaGreen, David Francis 1975. "Optimization of electrostatic binding free energy : applications to the analysis and design of ligand binding in protein complexes". Thesis, Massachusetts Institute of Technology, 2002. http://hdl.handle.net/1721.1/16888.
Pełny tekst źródłaVita.
Includes bibliographical references (p. 279-298).
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Electrostatic interactions play an important role in determining the energetics of association in biomolecular complexes. Previous work has shown that, within a continuum electrostatic model, for any given complex there exists a ligand charge distribution which optimizes the electrostatic binding free energy - the electrostatic complement of the target receptor. This electrostatic affinity optimization procedure was applied to several systems both in order to understand the role of electrostatic interactions in natural systems and as a tool in the design of ligands with improved affinity. Comparison of the natural and optimal charges of several ligands of glutaminyl-tRNA synthetase from E. coli, an enzyme with a strong natural requirement for specificity, shows remarkable similarity in many areas, suggesting that the optimization of electrostatic interactions played a role in the evolution of this system. The optimization procedure was also applied to the design of improvements to two inhibitors of HIV-1 viral-cell membrane fusion. Two tryptophan residues that are part of a D-peptide inhibitor were identified as contributing most significantly to binding, and a novel computational screening procedure based on the optimization methodology was developed to screen a library of tryptophan derivatives at both positions. Additionally, the optimization methodology was used to predict four mutations to standard amino acids at three positions on 5-Helix, a protein inhibitor of membrane fusion. All mutations were computed to improve the affinity of the inhibitor, with a five hundred-fold improvement calculated for one triple mutant.
(cont.) In the complex of b-lactamase inhibitor protein with TEM1 b-lactamase, a novel type of electrostatic interaction was identified, with surface exposed charged groups on the periphery of the binding interface projecting significant energetic effects through as much as 10 A of solvent. Finally, a large number of ab initio methods for determining partial atomic charges on small molecules were evaluated in terms of their ability to reproduce experimental values in continuum electrostatic calculations, with several preferred methods identified.
by David Francis Green.
Ph.D.
Keränen, Henrik. "Advances in Ligand Binding Predictions using Molecular Dynamics Simulations". Doctoral thesis, Uppsala universitet, Beräknings- och systembiologi, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-230777.
Pełny tekst źródłaNervall, Martin. "Binding Free Energy Calculations on Ligand-Receptor Complexes Applied to Malarial Protease Inhibitors". Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8338.
Pełny tekst źródłaMohamed, Noor Asidah Binti. "The evaluation of protein-ligand binding free energies using advanced potential energy function". Thesis, University of Southampton, 2018. https://eprints.soton.ac.uk/428049/.
Pełny tekst źródłaGobbo, Dorothea <1989>. "Free energy and kinetics in protein-ligand binding: experimental measurements and computational estimates". Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2019. http://amsdottorato.unibo.it/8982/1/Gobbo_Dorothea_tesi.pdf.
Pełny tekst źródłaNandigrami, Prithviraj. "Cooperative allosteric ligand binding in calmodulin". Kent State University / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=kent1507302866723977.
Pełny tekst źródłaCarlsson, Jens. "Challenges in Computational Biochemistry: Solvation and Ligand Binding". Doctoral thesis, Uppsala University, Department of Cell and Molecular Biology, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8738.
Pełny tekst źródłaAccurate calculations of free energies for molecular association and solvation are important for the understanding of biochemical processes, and are useful in many pharmaceutical applications. In this thesis, molecular dynamics (MD) simulations are used to calculate thermodynamic properties for solvation and ligand binding.
The thermodynamic integration technique is used to calculate pKa values for three aspartic acid residues in two different proteins. MD simulations are carried out in explicit and Generalized-Born continuum solvent. The calculated pKa values are in qualitative agreement with experiment in both cases. A combination of MD simulations and a continuum electrostatics method is applied to examine pKa shifts in wild-type and mutant epoxide hydrolase. The calculated pKa values support a model that can explain some of the pH dependent properties of this enzyme.
Development of the linear interaction energy (LIE) method for calculating solvation and binding free energies is presented. A new model for estimating the electrostatic term in the LIE method is derived and is shown to reproduce experimental free energies of hydration. An LIE method based on a continuum solvent representation is also developed and it is shown to reproduce binding free energies for inhibitors of a malaria enzyme. The possibility of using a combination of docking, MD and the LIE method to predict binding affinities for large datasets of ligands is also investigated. Good agreement with experiment is found for a set of non-nucleoside inhibitors of HIV-1 reverse transcriptase.
Approaches for decomposing solvation and binding free energies into enthalpic and entropic components are also examined. Methods for calculating the translational and rotational binding entropies for a ligand are presented. The possibility to calculate ion hydration free energies and entropies for alkali metal ions by using rigorous free energy techniques is also investigated and the results agree well with experimental data.
Sund, Johan. "From Structure to Function with Binding Free Energy Calculations for Codon Reading, Riboswitches and Lectins". Doctoral thesis, Uppsala universitet, Beräknings- och systembiologi, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-207140.
Pełny tekst źródłaAbdul, Rahim Nur Aida. "Investigating the mechanotransduction by two-photon fluorescence microscopy measurement of intracellular free energy of binding". Thesis, Massachusetts Institute of Technology, 2008. http://hdl.handle.net/1721.1/44746.
Pełny tekst źródłaIncludes bibliographical references (p. 99-108).
Force, due either to haemodynamic shear stress or relayed directly to the cell through adhesion complexes, is transmitted and translated into biological signals. This process is known as mechanotransduction. Extensive studies have been carried out on the signaling pathways involved in mechanotransduction. However, the mechanism(s) of mechanotransduction has yet to be fully understood. This thesis focuses on the measurement of the intracellular binding constant between focal adhesion proteins of interest, GFP-Paxillin and FAT-mCherry, using two-photon excitation fluorescence microscopy and the utility of it as a measure of protein conformational change. The hypothesis tested is that force-induced changes in protein conformation alter inter-protein binding affinity. A comprehensive toolkit that utilizes fluorescence microscopy techniques, Forster Resonance Energy Transfer (FRET) and its corollary, Fluorescence Lifetime Imaging (FLIM), as well as Fluorescence Correlation Spectroscopy (FCS), was developed. A procedure by which low photon counts cell data from FLIM could be included in global analysis fits and be corrected for was developed. This results in the recovery of maximum information from cellular data. Successful intracellular FCS measurements were combined with FLIM global analysis data to calculate the free energy of binding between GFP-Paxillin and FAT-mCherry. Results demonstrate that inter-cell heterogeneity exists and likely gives rise to differences in measured AIG. The application of these measurement techniques to cells experiencing 10% step strain shows that inter-protein binding is tighter upon stretch application. The source of this change is not clear, though Tyr phosphorylation has been ruled out by biochemical disruption of kinase activity.
by Nur Aida Abdul Rahim.
Ph.D.
Chen, Zhihong. "Modeling Ion Binding in the Chloride Transporter". University of Cincinnati / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1439310689.
Pełny tekst źródłaMiao, Yi. "Shape-Dependent Molecular Recognition of Specific Sequences of DNA by Heterocyclic Cations". Digital Archive @ GSU, 2006. http://digitalarchive.gsu.edu/chemistry_diss/4.
Pełny tekst źródłaGregor, Craig Robert. "Epitopes, aggregation and membrane binding : investigating the protein structure-function relationship". Thesis, University of Edinburgh, 2012. http://hdl.handle.net/1842/5833.
Pełny tekst źródłaGilabert, Navarro Joan Francesc. "Estimation of binding free energies with Monte Carlo atomistic simulations and enhanced sampling". Doctoral thesis, Universitat Politècnica de Catalunya, 2020. http://hdl.handle.net/10803/669282.
Pełny tekst źródłaEls grans avenços en la capacitat de computació han motivat l'esperança que els mètodes de simulacions per ordinador puguin accelerar el ritme de descobriment de nous fàrmacs. Per a què això sigui possible, es necessiten eines ràpides, acurades i fàcils d'utilitzar. Un dels problemes que han rebut més atenció és el de la predicció d'energies lliures d'unió entre proteïna i lligand. Dos grans problemes han estat identificats per a aquests mètodes: la falta de mostreig i les aproximacions dels models. Aquesta tesi està enfocada a resoldre el primer problema. Per a això, presentem el desenvolupament de mètodes eficients per a l'estimació de d'energies lliures d'unió entre proteïna i lligand. Hem desenvolupat un protocol que combina mètodes anomenats enhanced sampling amb simulació clàssiques per a obtenir una major eficiència. Els mètodes d'enhanced sampling són una classe d'eines que apliquen algun tipus de pertorbació externa al sistema que s'està estudiant per tal d'accelerar-ne el mostreig. En el nostre protocol, primer correm una simulació exploratòria d'enhanced sampling, començant per una mostra de la unió de la proteïna i el lligand. Aquesta simulació esta parcialment esbiaixada cap a aquells estats del sistema on els dos components es troben més separats. Després utilitzem la informació obtinguda d'aquesta primera simulació més curta per a córrer una segona simulació més llarga, amb mètodes sense biaix per obtenir una estadística fidedigna del sistema. Gràcies a la modularitat i el grau d'automatització que la implementació del protocol ofereix, hem pogut provar tres mètodes diferents per les simulacions llargues: PELE, dinàmica molecular i AdaptivePELE. PELE i dinàmica molecular han mostrat resultats similars, tot i que PELE utilitza menys recursos. Els dos han mostrat bons resultats en l'estudi de sistemes de fragments o amb proteïnes amb llocs d'unió poc flexibles. Però, els dos han fallat a l'hora de reproduir els resultats experimentals per a una quinasa, la Mitogen-activated protein kinase 1 (ERK2). D'altra banda, AdaptivePELE no ha mostrat una gran millora respecte a PELE, amb resultats positius per a la proteïna Urokinase-type plasminogen activator (URO) i una clara falta de mostreig per al receptor de progesterona (PR). En aquest treball hem demostrat la importància d'establir un banc de proves equilibrat durant el desenvolupament de nous mètodes. Mitjançant l'ús d'un banc de proves divers hem pogut establir en quins casos es pot esperar que el protocol obtingui resultats acurats, i quines àrees necessiten més desenvolupament. El banc de proves ha consistit de quatre proteïnes i més de trenta lligands, molt més dels que comunament s'utilitzen en el desenvolupament de mètodes per a la predicció d'energies d'unió mitjançant mètodes basats en camins (pathway-based). En resum, la metodologia desenvolupada durant aquesta tesi pot contribuir al procés de recerca de nous fàrmacs per a certs tipus de sistemes de proteïnes. Per a la resta, hem observat que els mètodes de simulació no esbiaixats no són prou eficients i tècniques més sofisticades són necessàries.
Almlöf, Martin. "Computational Methods for Calculation of Ligand-Receptor Binding Affinities Involving Protein and Nucleic Acid Complexes". Doctoral thesis, Uppsala University, Department of Cell and Molecular Biology, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7421.
Pełny tekst źródłaThe ability to accurately predict binding free energies from computer simulations is an invaluable resource in understanding biochemical processes and drug action. Several methods based on microscopic molecular dynamics simulations exist, and in this thesis the validation, application, and development of the linear interaction energy (LIE) method is presented.
For a test case of several hydrophobic ligands binding to P450cam it is found that the LIE parameters do not change when simulations are performed with three different force fields. The nonpolar contribution to binding of these ligands is best reproduced with a constant offset and a previously determined scaling of the van der Waals interactions.
A new methodology for prediction of binding free energies of protein-protein complexes is investigated and found to give excellent agreement with experimental results. In order to reproduce the nonpolar contribution to binding, a different scaling of the van der Waals interactions is neccesary (compared to small ligand binding) and found to be, in part, due to an electrostatic preorganization effect not present when binding small ligands.
A new treatment of the electrostatic contribution to binding is also proposed. In this new scheme, the chemical makeup of the ligand determines the scaling of the electrostatic ligand interaction energies. These scaling factors are calibrated using the electrostatic contribution to hydration free energies and proposed to be applicable to ligand binding.
The issue of codon-anticodon recognition on the ribosome is adressed using LIE. The calculated binding free energies are in excellent agreement with experimental results, and further predict that the Leu2 anticodon stem loop is about 10 times more stable than the Ser stem loop in complex with a ribosome loaded with the Phe UUU codon. The simulations also support the previously suggested roles of A1492, A1493, and G530 in the codon-anticodon recognition process.
Orro, Graña Adolfo. "Examination of the role of binding site water molecules in molecular recognition". Thesis, SciLifeLab Stockholm, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-200164.
Pełny tekst źródłaUciechowska, Urszula Sylwia [Verfasser], Wolfgang [Akademischer Betreuer] Sippl, Gerhard [Akademischer Betreuer] Wolber i Manfred [Akademischer Betreuer] Jung. "Virtual screening and binding free energy calculations of sirtuin inhibitors / Urszula Sylwia Uciechowska. Betreuer: Wolfgang Sippl ; Gerhard Wolber ; Manfred Jung". Halle, Saale : Universitäts- und Landesbibliothek Sachsen-Anhalt, 2010. http://d-nb.info/1025133943/34.
Pełny tekst źródłaGibson, Meghan E. "Examining the Role of Magnesium Ions in the Structural Stability of Ribosomal Subunits and An Investigation of a Novel Anticancer Therapeutic: Analyzing the Binding Affinity of a Stapled p53 Peptide Analog for Regulator MDM2". Thesis, Boston College, 2011. http://hdl.handle.net/2345/bc-ir:104431.
Pełny tekst źródłaComputational research can play a crucial component in the discovery of unique biochemical phenomena, from answering fundamental questions about molecular function and structure to the modeling of designed pharmaceuticals to cure many debilitating illnesses. Here computational methods are employed to examine the exquisite role that magnesium ions play in stabilizing ribosomal subunits responsible for protein translation and to analyze the potential of a proposed anticancer drug for a pathway that is impaired in the majority of human cancer cases
Thesis (BS) — Boston College, 2011
Submitted to: Boston College. College of Arts and Sciences
Discipline: College Honors Program
Discipline: Chemistry
Lind, Christoffer. "Computational Studies of Protein Synthesis on the Ribosome and Ligand Binding to Riboswitches". Doctoral thesis, Uppsala universitet, Beräkningsbiologi och bioinformatik, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-328583.
Pełny tekst źródłaShamsudin, Khan Yasmin. "Non-Steroidal Anti-Inflammatory Drugs in Cyclooxygenases 1 and 2 : Binding modes and mechanisms from computational methods and free energy calculations". Doctoral thesis, Uppsala universitet, Beräkningsbiologi och bioinformatik, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-328478.
Pełny tekst źródłaCook, Monica Mion. "Endocrine-Disrupting Compounds: Measurement in Tampa Bay, Removal from Sewage and Development of an Estrogen Receptor Model". Scholar Commons, 2015. http://scholarcommons.usf.edu/etd/5861.
Pełny tekst źródłaMontalvo, Acosta Joel José. "Computational approaches to molecular recognition : from host-guest to protein-ligand binding". Thesis, Strasbourg, 2018. http://www.theses.fr/2018STRAF051/document.
Pełny tekst źródłaMolecular recognition is a very interesting problem, and foremost, a current challenge for biophysical chemistry. Having reliable predictions on the specific recognition between molecules is highly priority as it will provide an insight of fundamental problems and will raise relevant technological applications. The dissertation presented here is centered on a quantitative analysis of molecular recognition in solution for host-guest, protein-ligand binding and catalysis. The statistical mechanics framework used to describe the state-of-the-art for receptor-ligand binding is an inflection point for the developing of new improved and methods. In fact, a highly performanced and accurate model was obtained for the analysis of host-guest binding. Finally, the presented models were used as a reliable predictive tools for discovering new chemical entities for enhance catalysis in solution
Berg, Emily Katherine. "Thermodynamics of λ-PCR Primer Design and Effective Ribosome Binding Sites". Thesis, Virginia Tech, 2019. http://hdl.handle.net/10919/89900.
Pełny tekst źródłaMaster of Science
Recombinant DNA technology has been used to genetically enhance organisms to produce greater amounts of a product already made by the organism or to make an organism synthesize a new product. Genes are commonly modified in organisms using cloning practices which typically involves inserting a target gene into a plasmid and transforming the plasmid into the organism of interest. A new cloning process developed in the Senger lab, λ-PCR, improves the cloning process compared to other methods due to its use of relatively inexpensive materials and high efficiency. A primary goal of this study was to develop a procedure for λ-PCR primer design that allows for accurate use of the cloning method. Additionally, this study investigated the use of synthetic ribosome binding sites to control and improve expression of proteins cloned into an organism. Ribosome binding sites are sequences located upstream of the gene that increase the molecule’s affinity for the rRNA sequence on the ribosome, bind to the ribosome just upstream of the beginning of the gene, and initiate expression of the gene. Tools have been developed that create synthetic ribosome binding sites designed to produce specific amounts of protein. For example, the tools can increase or decrease expression of a gene depending on the application. These tools, the Salis Lab RBS Calculator and NUPACK, were used to design and evaluate the effects of the synthetic ribosome binding sites. Additionally, a new method was created to design synthetic ribosome binding sites since the methods used during the design process yielded inaccuracies. Each strain of E. coli contained the same gene, a cyan fluorescent protein (CFP), but had different RBS sequences located upstream of the gene. Expression of CFP was controlled via induction, meaning the addition of a particular molecule, IPTG in this system, triggered expression of CFP. Each of the CFP strains were tested with a variety of v conditions in order to find the conditions most suitable for protein expression; the variables tested include: induction time, IPTG (inducer) concentration, and temperature. Media was also tested for the cell-free systems, meaning the strains were grown overnight for 18 hours and lysed, a process where the cell membrane is broken in order to utilize the cell’s components for protein expression; the cell lysate was resuspended in new media for the experiments. ANOVA and multiple linear regression revealed IPTG concentration, induction time, and media to be significant factors impacting protein expression. This analysis also showed each CFP strain did not perform as the RBS Calculator predicted. Modeling each strain’s CFP expression using the RBS-rRNA binding strengths and secondary structures present in the RBS allowed for the creation of a new model for predicting and designing RBS sequences.
Becker, Caroline [Verfasser], i Rainer [Akademischer Betreuer] Böckmann. "Development of computational methods for the prediction of protein structure, protein binding, and mutational effects using free energy calculations / Caroline Becker. Gutachter: Rainer Böckmann". Erlangen : Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2014. http://d-nb.info/1054331456/34.
Pełny tekst źródłaBoukharta, Lars. "Computational Modelling of Ligand Complexes with G-Protein Coupled Receptors, Ion Channels and Enzymes". Doctoral thesis, Uppsala universitet, Beräknings- och systembiologi, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-212103.
Pełny tekst źródłaDonnini, S. (Serena). "Computing free energies of protein-ligand association". Doctoral thesis, University of Oulu, 2007. http://urn.fi/urn:isbn:9789514285745.
Pełny tekst źródłaMackness, Brian C. "The Identification and Targeting of Partially-Folded Conformations on the Folding Free-Energy Landscapes of ALS-Linked Proteins for Therapeutic Intervention: A Dissertation". eScholarship@UMMS, 2016. https://escholarship.umassmed.edu/gsbs_diss/826.
Pełny tekst źródłaMackness, Brian C. "The Identification and Targeting of Partially-Folded Conformations on the Folding Free-Energy Landscapes of ALS-Linked Proteins for Therapeutic Intervention: A Dissertation". eScholarship@UMMS, 2004. http://escholarship.umassmed.edu/gsbs_diss/826.
Pełny tekst źródłaBuch, Mundó Ignasi 1984. "Investigation of protein-ligand interactions using high-throughput all-atom molecular dynamics simulations". Doctoral thesis, Universitat Pompeu Fabra, 2012. http://hdl.handle.net/10803/101407.
Pełny tekst źródłaSuciu, Ioana. "Energy aware optimization for low power radio technologies". Doctoral thesis, Universitat Politècnica de Catalunya, 2020. http://hdl.handle.net/10803/668889.
Pełny tekst źródłaEl crecimiento significativo de la IoT está empujando al mercado hacia el desarrollo de dispositivos de bajo coste, de muy bajo consumo energético y con un fuerte enfoque en la miniaturización, para aplicaciones que requieran sensores corporales, monitoreo de salud personal y micro-robots. La investigación en el campo de la eficiencia energética en la IoT propone soluciones que van desde la optimización de la capa física hasta la capa de red. Este trabajo se centra en explorar nuevas técnicas para mejorar la eficiencia energética y la experiencia del usuario de las redes IoT. Dividimos las técnicas propuestas en técnicas de optimización de nivel de trama de red y chip, respectivamente. Si bien las técnicas de nivel de trama están destinadas a mejorar el rendimiento de las tecnologías de radio existentes, las técnicas de nivel de chip tienen como objetivo reemplazarlas por arquitecturas que no requieren de cristales. Las técnicas de nivel de trama desarrolladas en este trabajo son el uso de autenticación de preámbulos y fragmentación de paquetes, aconsejables para redes LPWAN, una tecnología que ofrece un menor consumo de energía por servicio prestado, pero es vulnerable frente a los ataques de agotamiento de energía y no escalan frente la densificación. El uso de preámbulos autenticados entre los sensores y las pasarelas de enlace se convierte en un mecanismo de defensa contra el agotamiento del batería previsto por los atacantes. Demostramos experimentalmente que este enfoque puede reducir con un 91% el efecto de un ataque de agotamiento, aumentando la vida útil del dispositivo de menos de 0.24 años a 2.6 años. Los experimentos se llevaron a cabo utilizando nodos sensores de detección de carga, utilizados comercialmente para el control y monitoreo de infrastructura crítica. Aunque la técnica se ejemplifica en el estándar LoRaWAN, el uso de autenticación de preámbulo es extensible a cualquier protocolo inalámbrico. En esta tesis se muestra también que el uso de la fragmentación de paquetes a pesar de que el paquete se ajuste a la trama, reduce la probabilidad de colisiones mientras aumenta el número de usuarios en una red con restricciones de ciclos de transmisión. Mediante el uso de simulaciones en Matlab, se obtiene una mejora importante en el rendimiento de la red con la fragmentación, con un mayor impacto en redes más lentas y densas. Usando simulaciones NS3, demostramos que combinar la fragmentación de paquetes con el NACK en grupo se puede aumentar la confiabilidad de la red, al tiempo que se reduce la energía consumida para las retransmisiones, a costa de agregar pequeños encabezados a cada fragmento. Como técnica de nivel de chip, consideramos el uso de radios para la comunicación que no usan referencias de frecuencia externas como los osciladores basados en un cristal. Esto permitiría tener todos los elementos del sensor en una sola pieza de silicio, lo que lo hace incluso diez veces más eficiente energéticamente debido a la integración del chip. La consecuencia inmediata, en el uso de osciladores digitales en vez de cristales, es la pérdida de precisión de la comunicación y la capacidad de cambiar fácilmente los canales de comunicación. En este sentido, proponemos una secuencia de algoritmos y fases de sincronización de frecuencia que deben ser respetados por un dispositivo sin cristales para que pueda unirse a una red al encontrar el canal de baliza, sintetizar todos los canales de comunicación y luego mantener su precisión contra el cambio de temperatura. Los algoritmos propuestos no necesitan una sobrecarga de red adicional, ya que están utilizando la señalización de red existente. La evaluación se realiza en simulaciones y experimentalmente en una implementación prototipo de una radio sin cristal IEEE802.15.4. Los resultados obtenidos experimentalmente muestran una precisión inicial ligeramente superior a 40 ppm, que luego será corregida por el chip para que sea inferior a 40 ppm.
Andér, Martin. "Computational Analysis of Molecular Recognition Involving the Ribosome and a Voltage Gated K+ Channel". Doctoral thesis, Uppsala universitet, Institutionen för cell- och molekylärbiologi, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-101413.
Pełny tekst źródłaKamble, Sharad R. "Molecular interactions in pharmaceutical preformulation and supramolecular complexes. Structural properties governing drug-plasma protein binding and investigation of amino acids co-crystals". Thesis, University of Bradford, 2018. http://hdl.handle.net/10454/16882.
Pełny tekst źródłaAlonso, Hernan, i hernan alonso@anu edu au. "Computer Modelling and Simulations of Enzymes and their Mechanisms". The Australian National University. The John Curtin School of Medical Research, 2006. http://thesis.anu.edu.au./public/adt-ANU20061212.161155.
Pełny tekst źródłaShekfeh, Suhaib [Verfasser], Wolfgang [Akademischer Betreuer] Sippl, Gerhard [Akademischer Betreuer] Wolber i Maciej [Akademischer Betreuer] Baginski. "Virtual screening and end-point binding free energy methods for developing targeted cancer therapies : applications on acetyltransferases and protein kinases as case studies / Suhaib Shekfeh. Betreuer: Wolfgang Sippl ; Gerhard Wolber ; Maciej Baginski". Halle, Saale : Universitäts- und Landesbibliothek Sachsen-Anhalt, 2015. http://d-nb.info/1070585947/34.
Pełny tekst źródłaChen, Wei. "Molecular dynamics simulations of binding, unfolding, and global conformational changes of signaling and adhesion molecules". Diss., Atlanta, Ga. : Georgia Institute of Technology, 2009. http://hdl.handle.net/1853/28118.
Pełny tekst źródłaCommittee Chair: Zhu, Cheng; Committee Member: Harvey, Stephen; Committee Member: Hud, Nicholas; Committee Member: Zamir, Evan; Committee Member: Zhu, Ting.
Hernández, Alvarez Lilian [UNESP]. "Identification and characterization of cruzain allosteric inhibitors: a computer-aided approach". Universidade Estadual Paulista (UNESP), 2017. http://hdl.handle.net/11449/151919.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Trypanosoma cruzi é o agente causal da doença de Chagas, uma infecção negligenciada que afeta milhões de pessoas nas regiões tropicais. A maioria dos fármacos empregados no tratamento desta doença são altamente tóxicos e geram resistência. Na atualidade, o descobrimento de inibidores alostéricos é um tópico emergente dentro da área de desenho computacional de fármacos, pois promove a acessibilidade a medicamentos mais seletivos e menos tóxicos. Neste trabalho foi desenvolvida uma estratégia para a descoberta computacional de inibidores alostéricos a qual foi aplicada à cruzaína, a principal cisteíno protease do T. cruzi. A caracterização molecular da forma livre e ligada da cruzaína foi investigada através do ancoramento molecular, simulações de dinâmica molecular, cálculos de energia livre de ligação e construção de redes de interações entre resíduos. A partir da análise baseada na geometria das estruturas geradas na dinâmica molecular, foram detectados dois potenciais sítios alostéricos na cruzaína. Os resultados sugerem a existência de diferentes mecanismos de regulação exercidos pela ligação de inibidores diferentes no mesmo sítio alostérico. Além disso, foram identificados os resíduos que estabelecem os caminhos de transmissão de informação entre um dos sítios alostéricos identificado e o sítio ativo da enzima. O presente estudo é a primeira aproximação de desenho de inibidores alostéricos da cruzaína e serve para futuras intervenções farmacológicas. Esses resultados constituem uma base para o desenho de inibidores específicos de cisteíno proteases homólogas da papaína.
Trypanosoma cruzi is the causative agent of Chagas disease, a neglected infection affecting millions of people in tropical regions. There are several chemotherapeutic agents for the treatment of this disease, but most of them are highly toxic and generate resistance. Currently, the development of allosteric inhibitors constitutes a promising research field, since it may improve the accessibility to more selective and less toxic medicines. To date, the allosteric drugs prediction is a state-of-the-art topic in rational structure-based computational design. In this work a simulation strategy was developed for computational discovery of allosteric inhibitors, and it was applied for or cruzain, a promising target and the major cysteine protease of T. cruzi. Molecular dynamics simulations, binding free energy calculations and network-based modelling of residue interactions were combined to characterize and compare molecular distinctive features of the apo form and the cruzain-allosteric inhibitor complexes. By using geometry-based detection on trajectory snapshots we determined the existence of two main allosteric sites suitable for drug targeting. The results suggest dissimilar mechanism exerted by the same allosteric site when binding different potential allosteric inhibitors. Finally, we identified the residues involved in suboptimal paths linking the identified site and the orthosteric site. The present study constitutes the first approximation for designing cruzain allosteric inhibitors and may serve for future pharmacological intervention. These findings are particularly relevant for the design of allosteric modulators of papain-like cysteine proteases.
CAPES: 031/2013
Domin, Gesine, Sven Findeiß, Manja Wachsmuth, Sebastian Will, Peter F. Stadler i Mario Mörl. "Applicability of a computational design approach for synthetic riboswitches". Universitätsbibliothek Leipzig, 2017. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-218007.
Pełny tekst źródłaDomin, Gesine, Sven Findeiß, Manja Wachsmuth, Sebastian Will, Peter F. Stadler i Mario Mörl. "Applicability of a computational design approach for synthetic riboswitches". Oxford University Press, 2016. https://ul.qucosa.de/id/qucosa%3A15259.
Pełny tekst źródłaBessoud, Agnès. "Analyse des interactions dans des alliages à base de métaux de transition". Grenoble INPG, 1989. http://www.theses.fr/1989INPG0091.
Pełny tekst źródłaChen, Po-Chin, i 陳博晉. "Computation of Binding Free Energy of Inhibitor-Erk Kinase Complexs Using Thermodynamic Integration Molecular Dynamics Simulation". Thesis, 2011. http://ndltd.ncl.edu.tw/handle/31597834109755377411.
Pełny tekst źródła國立臺灣師範大學
化學系
100
Erk is the downstream protein in the Ras/Raf/MEK/ERK signal transduction pathway which is deregulated in many cancers. In the present study, we select this kinase to design new inhibitors for this kinase using MD simulation. Previous computations have shown that thermodynamic integration (TI) MD simulation method is able to give relative binding free energy for a pair of inhibitors for this kinase in good agreement with experimental results. In the present study, we carried out TI-MD computations for new analogous compounds in searching for better inhibitors. An analog with –OH functional group on the benzene ring was found to have better affinity than the 82A ligand by 1.1 kcal/mol. In addition, we investigate how single mutational step performs compared with the triple mutational steps in the TI-MD method. Furthermore, effect of number of lambda points in the computed relative binding free energy was investigated as well. These results should be useful for further TI-MD simulation and inhibitor design of this kind.
Chang, Jeng-Yih, i 張正義. "Study of the Aggregation of β-amyloid Peptide (Aβ) : Monte Carlo Simulations and Binding Free Energy Calculations". Thesis, 2008. http://ndltd.ncl.edu.tw/handle/71038099971134684738.
Pełny tekst źródła國立陽明大學
生物醫學資訊研究所
96
Alzheimer's disease (AD) is the most common form of dementia in aged population. It gradually impairs patients' memory, cognition, and behavior. One of the molecular pathology of this disease is defined by the presence within the brain of senile plaques. The senile plaques are made of deposits of the β-amyloid peptide (Aβ). Generally, Aβ can be dissolved in water and exists as a random coil conformation. However, under certain conditions, Aβ will form aggregates of β-sheets. Then, these aggregates are arranged as insoluble fibrils which cause neurotoxicity. Previous studies indicate that mutations will affect the aggregation ability of Aβ. When Leu17 and Phe19 are mutated to Ala, the aggregation rate of Aβ will be decreased in water. But another mutation of Glu22 to Gly (Dutch mutant) forms protofibrils more rapidly than wild type. Here we use Monte Carlo simulation and binding free energy calculation to investigate the differences between the Aβ (L17A/F19A) mutant, Aβ (E22G) mutant and Aβ wild type. Aβ (L17A/F19A) mutant shows a lower probability to form β-sheet stacking in Monte Carlo simulation. In addition, the binding free energy of Aβ (L17A/F19A) mutant is also higher than that of Aβ wild type. These results mean that the Aβ (L17A/F19A) mutant is more difficult to form aggregates of β-sheets. But Aβ (E22G) mutant is different with Aβ (L17A/F19A) mutant. The binding free energy of Aβ (E22G) mutant is lower than that of Aβ wild type. So Aβ (E22G) mutant is easier to aggregate. The results of this study are in good agreement with previous experimental studies.