Biomolecular chemical simulations have recently become useful as a research method in the fields of organic chemistry and bioscience. Recently we have focused our attention on the biomolecular computational simulation of lipase enzyme-ligand complexes to predict the enantioselectivity and reactivity of lipases toward non-natural organic compounds. In this paper, we describe the molecular simulations such as molecular dynamics (MD) and fragment molecular orbital (FMO) calculations for the complexes of Candida antarctica lipase typeA (CALA) and trifluoromethylazulene alcohol derivatives. The MD calculations show that for esters with high enantioselectivity, the fast-reacting enantiomer of esters is located near the active site of CALA, whereas the slow reacting enantiomer of esters moves away from the active site of CALA. On the other hand, for the esters with low enantioselectivity, we found that both (R)- and (S)-enantiomers of esters remain the active site of CALA. The FMO computations indicate that for the esters with high enantioselectivity, each fast-reacting enantiomer shows strong interactions with some particular amino acid residues, including Asp95, whereas for the esters with low enantioselectivity, both (R)- and (S)-enantiomers interact with identical amino acid residues including Asp95. It is predictable that Asp95 in CALA plays an important role in the chiral recognition of enantiomers through lipase-catalyzed biotransformations.
