Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 17 of 17 for “"Free energy perturbation"”.
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On free energy calculations using fluctuation theorems of work
… Ältere stochastische Methoden wie R. Zwanzig's Free Energy Perturbation und Ch. Bennett's Acceptance Ratio Methode wurden jüngst unter Ausnutzung der Jarzynski Gleichung und des Crooks'schen Fluktuationstheoremes verallgemeinert und verknüpfen derart die Verteilung der in einem …
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Bridging molecular and systems scales in membrane biology
… with umbrella sampling (US), and Alchemical Free-Energy Perturbation (Alchemical FEP) to study how the structural changes associated with point mutations affect mechanical aspects of conformational change in channels, such as hERG (Chapter 5), and the ability of growth factors to bind and …
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Molecular dynamics studies of membranes and membrane proteins
… by combining molecular dynamics simulations, free energy perturbation theory and continuum electrostatics calculations. Three systems were investigated: (1) The proton pump cycle of the integral membrane protein bacteriorhodopsin: The photoisomerization and subsequent thermal reactions of the …
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THE USE OF EXPANDED ENSEMBLE FOR THE PREDICTION OF WATER-ORGANIC SOLVENT PARTITION COEFFICIENTS OF SMALL DRUG-LIKE MOLECULES
… has become a central focus in drug discovery. Free Energy Perturbation (FEP) methods are popular molecular mechanics approaches for predicting logP values. However, challenges remain, including sensitivity to force field choice and difficulties in adequately sampling complex free energy …
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Computational investigation of membrane proteins across species and functional classes
… 2J2 using molecular docking, MD simulations, and free energy perturbation calculations, elucidating structural determinants governing regioselective cannabinoid metabolism. Next, I examine lipid-dependent stabilization of the ATP-binding cassette transporter BmrCD from Bacillus subtilis, showing …
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Computer simulation of free energies to predict cis/trans equilibria of prolyl peptides and solvation free energies of phenylalanyl peptides
… of small peptides (Part II). In Part I, the free energy perturbation (FEP) method, using AMBER, was utilized to calculate the Gibbs free energy difference between <i>cis</i> and <i>trans</i> conformers of Ace-Tyr-Pro- NMe and Ace-Asn-Pro-NMe, from which the ratio of <i>cis</i> to <i>trans</i> …
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Decompositions of Free Energies in Molecular Simulation
… thesis describes advances in methods to measure free energy changes in simulations of molecular systems. In each case the free energy is decomposed into local environments which reveal insights about the complex systems being studied. Free energy is a fundamental quantity that can be used to …
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COMPUTATIONAL APPROACHES FOR PROTEIN FOLDING AND LIGAND BINDING: FROM THERMODYNAMICS TO KINETICS
… approaches. Alchemical methods, including free energy perturbation (FEP) and thermodynamic integration (TI), have become the dominant method for computing high-quality estimates of protein-ligand binding free energies. In particular, the widely-used approach of relative binding free energy …
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The Dynamics of Dehydrogenases - A Phase Space Odyssey
… necessitated by transition state theory or free energy perturbation methods. It was found that this method could calculate the primary H/D kinetic isotope effect of the conversion of benzyl alcohol to benzaldehyde in yeast alcohol dehydrogenase to within the margin of error of experimentally …
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The Atom Surface Site Interaction Point Approach to Non-Covalent Interactions
… whole. The description has been tested with the free energy of transfer from n-hexadecane to water and showed good systematic prediction of phase transfer (RMSD of 5.2 kJ mol<sup>-1</sup>). To consider interactions between two small molecules, we developed a custom pairing algorithm which …
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MARKOV STATE MODELS AND THEIR APPLICATIONS IN PROTEIN FOLDING SIMULATION, SMALL MOLECULE DESIGN, AND MEMBRANE PROTEIN MODELING
… or external (such as high temperature) perturbation that obstructs three-dimensional structure of a protein will also interfere with its function. Many diseases are associated with inability of protein to form its unique structure. For example, sickle cell anemia is caused by a single …
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Monte Carlo Simulation Methods for Studying the Thermodynamics of Ligand Binding & Transfer Processes in Biomolecules
… important for the understanding of bioenergetic energy transduction. The results of this thesis are presented in five articles that are published in peer reviewed scientific journals. Manuscript A presents the Monte Carlo simulation software GMCT which was largely developed in this thesis. The …
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Multiscale Modeling of the Mechanical Behavior of Clay
… between pairs of primary clay particles using a free energy perturbation method. We compare results for two commonly occurring clay minerals, illite and Na-smectite, both with 2:1 sheet structures, and nanotubular imogolite (1:1). Illite particles exhibit a well-defined potential well at 11 Å …
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Ion Pairing in Aqueous Metal Sulfates and Platinum Group Metal Ammonium Solutions
… force calculations are used to provide ion pair free energy profiles and free energy perturbation calculations are used to calibrate the potential of mean force (PMF) from which association constants for ion pairs can be produced for these metal sulfate solutions. The calibrated free energy …
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Towards more robust and efficient methods for the calculation of Protein-Ligand binding affinities
… that should be accurate in principle, such as free energy perturbation (FEP) theory, to relatively simple approximations based on empirically derived scoring functions, the counterbalancing demands of speed and accuracy have left us with no completely satisfactory solution thus far. This thesis …
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Structural and Mechanistic Studies of Multidrug Resistance Efflux Pumps in Multiple Families
… complex, we developed and optimized a detergent-free purification protocol for structural analysis by cryogenic election microscopy. To explore its mobility within the cellular milieu, we also attempted to cross-link the complex with the peptidoglycan layer in an effort to identify points of …
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Structural Basis for the Molecular Recognition of Androgen Receptor Ligands: Insights Guiding the Design and Synthesis of Novel Nonsteroidal Ligands
… model refinement offers advantages over minimal energy-based methods.</p> <p>The binding modes of several hydroxyflutamide-like nonsteroidal ligands for the AR were investigated. These nonsteroidal ligands were docked into one of our AR models with FlexX, followed by refinement of the initial …