Electrostatic enhancement of protein-protein association rate predicted from a transition-state model.

Protein-protein association is central to most protein functions. The rate of association is limited by the translational and rotational diffusion that brings the two proteins into their bound configuration. Electrostatic interactions between the protein partners can enhance an otherwise low rate resulting from the stereospecificity of the association. Based on the idea that the asynchronous decrease in translational/rotational entropy and the free energy of interactions leads to a free-energy barrier, a transition-state theory for association has been proposed [Vijayakumar et al. (J. Mol. Biol, 1998); Zhou (Biopolymers, 2001)]. Here we further develop and test this theory. The model for the transition state is built from the dependence of native contacts on translation/rotational degrees of freedom. The predicted electrostatic rate enhancement is found to agree well with experimental data for the effects of ionic strength and charge mutations on the association of barnase and barstar.