The empirical valence bond as an effective strategy for computer-aided enzyme design

Abstract

The ability of the empirical valence bond (EVB) to be used in screening active site residues in enzyme design is explored in a preliminary way. This validation is done by comparing the ability of this approach to evaluate the catalytic contributions of various residues in chorismate mutase. It is demonstrated that the EVB model can serve as an accurate tool in the final stages of computer-aided enzyme design (CAED). The ability of the model to predict quantitatively the catalytic power of enzymes should augment the capacity of current approaches for enzyme design.

Figure 1

Scheme of the Chorismate Mutase active site. The figure shows the structure of the transition state and its interactions with the neighboring residues, (a) for the dimer and monomer and (b) for the trimer.

Figure 2

Correlation between the calculated and observed activation free energies.