Intermolecular Modeling Methods in Drug Design/Modeling the Mechanism of Peptide Cleavage by Thermolysin

Abstract

As an outgrowth of our small molecule modeling effort, we have begun to develop a large molecule modeling system. This new effort centers around a VAX 11/780 coupled to an Evans and Sutherland Color Multi-Picture system. The software currently available is A. Jones' FRODO program for display and manipulation, M. Connolly's SURFACE program, A. Hagler's VFF energy calculation program, and a variety of small programs written in-house. The structure and capabilities of this system will be described. An application of the system to studying the mechanism of peptide cleavage by the zinc endopeptidase thermolysin will be presented. This investigation has led us to suggest a number of modifications to the previously proposed mechanism and offers a rationalization for published substrate data.

Keywords

Merck Molecular Modeling System (MMMS)Computational chemistry Computer graphics Mechanism Thermolysin Zinc peptidase

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