Energy profiles for the rate-limiting stage of the serine protease prototype reaction

The energy profiles of reaction, modeling the rate-limiting stage of serine protease catalyzed transformations, have been computed by quantum chemistry, methods. The model includes fragments of the residues of the catalytic triad (serine, histidine, and aspartic acid), two water molecules as an oxyanion hole, represented by effective fragment potentials, and a formamide molecule as a substrate. Geometry optimizations have been performed along the reaction coordinate, chosen as the distance between oxygen of serine and carbon of substrate, by using the Hartree-Fock method. The density functional theory B3LYP/6-31+G(d,p) calculations have been employed to recalculate energies along the reaction path in the gas phase and in the dielectric environment. The computed barrier heights are fairly consistent with the data cited in the literature. (C) 2002 Wiley Periodicals, Inc.

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