All-Electron Computational Simulations for the Enantiopreference of Lipase Enzyme with Fragment Molecular Orbital Method

Abstract

We are exclusively utilizing biomolecules, such as enzyme proteins and carbohydrates, in the fields of organic synthesis and bioorganic chemistry. Recently we have focused our attention on computational simulations of lipase enzymes and lipase-ligand complexes to understand and predict the substrate specificity and enantioselectivity of lipases toward non-natural organic compounds on the basis of quantum theory. In this work, Candida antarctica lipase typeB (CALB)-secondary alcohol ester complexes, which were refined by both continuum and explicit solvent models for water, were computed using ab initio fragment molecular orbital (FMO) calculations at MP2/STO-3G level. The all-electron FMO calculations showed that the binding energy for the fast reacting (R)-ester is negatively larger than that for the slow reacting (S)-ester. It is also found that the interaction energies between Thr40 residue in the CALB complexes and the ester substrates are large compared to those between the catalytic triad of CALB, Ser105, Asp187, and His224 residues, and the substrates. The difference for the binding energy clearly points out that the enantiopreference of lipases toward organic compounds is capable of predicting by employing computational simulations with quantum chemical calculations.