ELECTROSTATIC ENHANCEMENT OF DIFFUSION-CONTROLLED PROTEIN-PROTEIN ASSOCIATION - COMPARISON OF THEORY AND EXPERIMENT ON BARNASE AND BARSTAR

The electrostatic enhancement of the association rate of barnase and b arstar is calculated using a transition-state theory like expression a nd atomic-detail modeling of the protein molecules. This expression pr edicts that the rate enhancement is simply the average Boltzmann facto r in the region of configurational space where association occurs inst antaneously in the diffusion-controlled limit. Based on experimental e vidence, this ''transition state'' is defined by configurations in whi ch, relative to the stereospecifically bound complex, the two proteins are shifted apart by similar to 8 Angstrom (so a layer of water can b e accommodated in the interface) and the two binding surfaces are rota ted away by 0 degrees to 3 degrees. The values of the average Boltzman n factor, calculated by solving the Poisson-Boltzmann equation, for th e wild-type complex and 16 complexes with single mutations are found t o correlate well with experimental results for the electrostatic rate enhancement. The predicted rate enhancement is found to be somewhat in sensitive to the precise definition of the transition state, due to th e long-range nature of electrostatic interactions. The experimental io nic strength dependence of the rate enhancement is also reasonably rep roduced. (C) 1998 Academic Press Limited.