Fragment molecular orbital calculations of protein-organic substrate compound complexes - application toward enzyme-catalyzed biotransformations and drug design -

Abstract

This presentation describes the applications of fragment molecular orbital (FMO) calculations to the elucidation of the mechanism for enzyme-catalyzed reactions in organic synthesis and the computational molecular design of pharmaceuticals. The molecular interactions, based on FMO2-MP2/6-31G calculations, between each of three different lipases, Burkholderia cepacia lipase (BCL), Candida antarctica lipase typeB (CALB), and Candida antarctica lipase typeA (CALA), and the enantiomers of various organic compounds indicated that particular amino acid residues in the respective lipases, such as HIS286 in BCL, THR40 in CALB, and ASP95 in CALA, can play an important role in the chiral recognition of substrate enantiomers. A group of computational life science researchers has established FMO Drug Design(FMODD) consortium in November 2014 that aims to demonstrate the availability of the FMO method as a novel technique for in silico drug design. The activities of FMODD and our FMO calculations on a target protein, renin, with the K computer will also be presented.