Application of structure-based thermodynamic calculations to the rationalization of the enantioselectivity of subtilisin in organic solvents

The effect of organic solvents on the selectivity of lyophilized or CLEC (cross-linked enzyme crystals)-subtilisin in the resolution of sec-phenethyl alcohol and trans-sobrerol was studied. A theoretical model, that tries to predict solvent effects on enantioselectivity only as a function of the activity coefficients of the desolvated part of the substrate in the relevant transition state of the reaction (Ke, T.; Wescott, C. R.; Klibanov, A. M. J. Am. Chem. Sec., 1996, 118, 3366) was examined and shown to agree poorly with the experimental data. The tetrahedral intermediate was studied with MonteCarlo molecular mechanics, and the activity coefficients were calculated with UNIFAC. (C) 1998 Elsevier Science Ltd. All rights reserved.