The catalyzed reaction of (R,S)-1-phenylethanol and S-ethyl thio-octanoate by lipase B from Candida antarctica is studied using density functional theory. Quantum mechanics cluster approach is used to model the enzyme's active site. The results show that the catalytic triad amino acids of the enzyme do not abstract the alcoholic proton of 1-phenylethanol before a nucleophilic attack from the alcohol to the ester. A twostep mechanism is proposed for the reaction of R-enantiomer of the alcohol with the ester. However, the results show no path for the S-enantiomer. We showed that enantioselectivity of the enzyme is due to di_erent hydrogen-bonding patterns of the two enantiomers of the alcohol in the enzyme's active site. The OH group of R-enantiomer is directed toward Ser-105, while the OH group of S-enantiomer is far from Ser-105 and is directed toward Thr-40.
