Enhancement of protein-protein association rate by interaction potential: accuracy of prediction based on local Boltzmann factor.

Electrostatic interactions are known experimentally to enhance the rate of protein-protein association by three to four orders of magnitude. However, theoretical efforts to quantitatively account for such rate enhancement have been hampered by the need to consider a large number of relative configurations of two associating proteins sampled during their diffusional encounter. Our recent work indicates that a good estimate of the rate enhancement is given by the average Boltzmann factor in the region of configurational space where association can effectively take place. This estimate is tested on a model system consisting of two spherical proteins, each with a "reactive patch." Three different forms of interaction potential are considered. Comparison with exact results for the association rate constant demonstrates that predictions based on the local Boltzmann factor are accurate to within approximately 50% for realistic sizes of the reactive region and amplitudes of the interaction potential.