COLLABORATION IN BASIC SCIENCE AND ENGINEERING (COBASE)

Steve Scheiner hosted Alex Isaev of the N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, from May to October 1999. Their project focused on quantum chemical methods used to probe the underlying mechanisms by which enzymes facilitate chemical reactions. Specifically, the scientific objectives of this project were: (1) to construct a model enzyme/substrate complex explaining lower activation barrier in formation of products, compared to analogous solution reactions, on the basis of the rearrangement of the H-bond network structure in the enzyme during the reaction; (2) to develop new concepts explaining the enzyme specificity as the result of specific solvation of the transition state (TS) where the mechanism of TS stabilization is determined by the increase in the mobility of the protons of H-bonds forming a network; and (3) to elucidate, within the bounds of the TS stabilization concept, molecular mechanism of energy redistribution in the H-bond network accompanied by the distortion (relaxation) of the AS structure in interaction of enzyme with substrate with the reaction rate enhancement and the significance of orientation and solvation effects. Both Scheiner and Isaev have benefited from this joint project. Each scientist had his own individual areas of expertise, which were combined nicely in this project. Isaev has an impressive background in enzyme mechanisms and Scheiner has expertise in monitoring proton transfer reactions from a quantum chemical perspective. By collaborating on this project, each scientist’s knowledge of the other’s field of expertise has expanded.