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ABSTRACT
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Abstract We applied the recently developed Neglect of Diatomic Differential Overlap Fragment Self-Consistent Field Monte Carlo method to the simulation of the liquid state of chlorinated monosilanes. This semiempirical technique divides... more
Abstract We applied the recently developed Neglect of Diatomic Differential Overlap Fragment Self-Consistent Field Monte Carlo method to the simulation of the liquid state of chlorinated monosilanes. This semiempirical technique divides the periodic simulation ...
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The catalytic properties of enzymes, containing the Asp-His-Ser triads are deeply investigated for a long time. Serine endopeptidases, cutinases, acetylcholinesterases, cellulases, among other enzymes, contain these triads. We found that... more
The catalytic properties of enzymes, containing the Asp-His-Ser triads are deeply investigated for a long time. Serine endopeptidases, cutinases, acetylcholinesterases, cellulases, among other enzymes, contain these triads. We found that solely the geometric properties of just four points in the spatial structure of these enzymes are characteristic to their family (Fig. 3).
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Research Interests: Structural Biology, Catalysis, Kinetics, Macromolecular X-Ray Crystallography, Crystal structure, and 11 moreEnzyme, Hydrogen Bond, Anions, Hydrogen Bonding, Active site, Amino Acid Substitution Rates, X Ray Crystallography, Serine Protease, Binding Site, Catalytic Activity, and Biochemistry and cell biology
A three dimensional structural model of oligopeptidase B (OpB) was constructed by homology modeling. High resolution X-ray structure of prolyl oligopeptidase (PEP), the only protein with sequential and functional homology was used as a... more
A three dimensional structural model of oligopeptidase B (OpB) was constructed by homology modeling. High resolution X-ray structure of prolyl oligopeptidase (PEP), the only protein with sequential and functional homology was used as a template. Initial models of OpB were built by the MODELLER and were analysed by the PROCHECK programs. The best quality model was chosen for further refinement by two different techniques--either constrained molecular dynamics simulations or simulated annealing calculations starting from 500 K. The overall quality of each of the refined models was evaluated and the simulated annealing procedure found to be more effective. The refined model was analysed by different protein analysis programs including PROCHECK for the evaluation of the Ramachandran plot quality, PROSA for testing interaction energies and WHATIF for the calculation of packing quality. This structure was found to be satisfactory and also stable at room temperature as demonstrated by a 300 ps long unconstrained molecular dynamics simulation. Calculation of molecular electrostatic potentials revealed that the binding site of OpB is more negative than that of PEP, in accordance with the experimentally observed selectivity of OpB towards proteolysis at dibasic sites. A recently developed Monte Carlo docking method was used provide a structural rationale for the affinity differences measured between Z-Arg and Z-Arg-Arg substrates.
Research Interests: Catalysis, Simulated Annealing, Monte Carlo, Macromolecular X-Ray Crystallography, Homology Modeling, and 16 moreComputer Software, Sequence alignment, Computer Simulation, Molecular Graphics, Enzyme, High Resolution, Protein Secondary Structure Prediction, Room Temperature, Three Dimensional, THEORETICAL AND COMPUTATIONAL CHEMISTRY, Amino Acid Sequence, Quality Model, Molecular Dynamic Simulation, Binding Site, Structural model, and Biochemistry and cell biology
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Research Interests: Molecular Biology, Macromolecular X-Ray Crystallography, Molecular, Crystal structure, Animals, and 12 moreTrypsin, Root-Mean Square Error, Enzyme, Rats, Protein Conformation, Amino Acid Sequence, Recombinant Proteins, X Ray Crystallography, Site-directed Mutagenesis, Binding Site, Biochemistry and cell biology, and Chymotrypsin
Three novel, N-acyl-pro-pyrrolidine-type, inhibitors of prolyl oligopeptidase (POP) with nanomolar activities were synthesized and their binding analyzed to the host enzyme in the light of X-ray diffraction and molecular modeling studies.... more
Three novel, N-acyl-pro-pyrrolidine-type, inhibitors of prolyl oligopeptidase (POP) with nanomolar activities were synthesized and their binding analyzed to the host enzyme in the light of X-ray diffraction and molecular modeling studies. We were interested in the alteration in the binding affinity at the S3 site as a function of the properties of the N-terminal group of the inhibitors. Our studies revealed that, for inhibitors with flat aromatic terminal groups, the optimal length of the linker chain is three C-C bonds, but this increases to four C-C bonds if there is a bulky group in the terminal position. Molecular dynamics calculations indicate that this is due to the better fit into the binding pocket. A 4-fold enhancement of the inhibitor activity upon replacement of the 4-CH2 group of the proline ring by CF2 is a consequence of a weak hydrogen bond formed between the fluorine atom and the hydroxy group of Tyr473 of the host enzyme. There is notably good agreement between the calculated and experimental free energies of binding; the average error in the IC50 values is around 1 order of magnitude.