Quantum mechanical modeling of aspartic proteinase interactions: difference in binding of diastereomeric statine models.
Quantum mechanical calculations were carried out for the interaction of two diastereomeric model inhibitors of aspartic proteinases with a model for the active site, based on crystallographic coordinates of endothiapepsin. The model inhibitor is formamide N-(2-hydroxy 3-methyl propane) and the active site is represented by the full backbone and most of the side chains of the two partial sequences D32-T33-G34-S35 and D215-T216-G217-T218. Those calculations demonstrate that the best binding mode for this short inhibitor is consistent with the X-ray experiments and somewhat stronger with the inhibitor in a 2(S) configuration, compared to 2(R). Another binding mode is possible for this model inhibitor only in the 2(S)-configuration, and is weaker than the first.
Goldblum
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Department of Pharmaceutical Chemistry, School of Pharmacy, Hebrew University of Jerusalem, Israel.
D000596:Amino Acids / Q000494:pharmacology*; D016282:Aspartic Acid Endopeptidases; D001665:Binding Sites; D003196:Computer Graphics; D003198:Computer Simulation; D010450:Endopeptidases; D006860:Hydrogen Bonding; D008958:Models, Molecular; D011480:Protease Inhibitors; D013237:Stereoisomerism; D013816:Thermodynamics
D000596:Amino Acids; D011480:Protease Inhibitors; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C042466:Endothia aspartic proteinase; C013165:statine