DESIGN OF FAST ENZYMES BY OPTIMIZING INTERACTION POTENTIAL IN ACTIVE-SITE

The diffusional encounter between substrate and enzyme, and hence cata lytic efficiency, can be enhanced by mutating charged residues on the surface of the enzyme. In this paper we present a simple method for sc reening such mutations. This is based on our earlier result that elect rostatic enhancement of the enzyme-substrate binding rate constant can be accounted for just by the interaction potential within the active site, Assuming that catalytic and structural integrity is maintained, the catalytic efficiency can be optimized by surface charge mutations which lead to stronger interaction potential within the active site, A pplication of the screening method on superoxide dismutase shows that only charge mutations close to the active site will have practical eff ect on the catalytic efficiency, This rationalizes a large number of f indings obtained in previous simulation and experimental studies.