Computational molecular simulations have recently become useful as a research method in the fields of organic chemistry and bioscience. In this paper, we carried out molecular dynamics (MD) calculations on the complexes of Burkholderia cepacia lipase (BCL) and Candida antarctica lipase typeB (CALB) with twelve different secondary and eight different primary alcohol esters to predict clearly lipase enantioselectivity toward non-natural organic compounds. We computed the C-O interatomic distance, RC-O, between the carbonyl carbon of ester and the oxygen of the active site amino acid residue (BCL: Ser87, CALB: Ser105) side chain OH in each lipase-ester complex. The MD computations show that RC-O for the fast reacting enantiomer of substrate esters remains roughly unchanged, while RC-O for the slow reacting enantiomer of esters increases with the elapsed time. In addition, we found that for the esters of high enantioselectivity (BCL: E >70, CALB: E >150), the difference in the RC-O between (R)- and (S)-ester complexes, ΔRC-O, is more than 9.0Å for BCL-ester complexes and 5.0Å for CALB-ester complexes. On the other hand, for the esters of low enantioselectivity, it is expected that ΔRC-O for each ester are correlated to E values for the corresponding esters. We have reached a conclusion that biomolecular computational simulations are useful tools for predicting and understanding the reactivity and the enantioselectivity of lipase-catalyzed biotransformations.
