Computer-assisted analysis of bioactivity. II. - The interaction of lactone suicide substrates with α-chymotrypsin

S. Naruto, I. Motoc, G. R. Marshall

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Three-dimensional interaction pattern of three lactone enzyme-activated irreversible inhibitors with a 115 non-hydrogen atoms active site model of α-chymotrypsin is studied using computer graphics combined with molecular mechanics. Systematic conformational analysis and energy minimization of the lactone in the active site were performed at two stages: (i) the non-covalent substrate complex, and (ii) the suicide compound. The calculations show that estimates of the van der Waals interaction energy correlate with the inactivation binding constants, K(m), and the final suicide conformation can be effectively assumed by the compounds considered. The present results corroborate our previous calculations and indicate that the approach used is of interest in guiding in the synthesis of new inhibitors.

Original languageEnglish
Pages (from-to)533-540
Number of pages8
JournalEuropean Journal of Medicinal Chemistry
Volume20
Issue number6
StatePublished - 1985

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