The Computer Graphics Laboratory facilities were used to display and analyze the molecular dynamics simulations results. My research projects focus on a) further refining and testing the new generation of additive and nonadditive force field parameters to be used in molecular mechanics and dynamics calculations. b) macromolecular simulation using molecular dynamics. A new set of charges, obtained using RESP approach, has been applied to study the influence of variety substituents in dioxane molecule on its conformational equilibria. The agreement with experimental NMR results were very successful. The second generation of the AMBER force field was finally completed and published. The new force field was extensively tested in molecular dynamics simulations for large molecules, with special focus on drug design. I performed free energy derivatives simulations for malarial protease inhibitors. This new technique allows us to predict in which direction malarial protease inhibitors should be chemically modified in order to achieve their better binding properties. The similar approach together with free energy perturbation calculations have been applied in elucidating the role of the peptide mimetics in inhibiting of the HIV aspartic protease. The peptide mimetics which we were the most interested in were modified derivatives of the JG-365 inhibitor where peptide bonds were replaced by ethylene or fluoro-ethylene units. Few replacement of this kind could potentially lead to increased inhibition potency.
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