DYNAMICS OF PROTEIN-PROTEIN DOCKING - CYTOCHROME-C AND CYTOCHROME-C PEROXIDASE REVISITED

The dynamics of the docking step in the electron transfer reaction bet ween yeast cytochrome c peroxidase and iso-1-cytochrome c has been stu died using the Brownian dynamics method. In particular we have calcula ted the bimolecular rate constant at which a specific complex, the xra y crystalline complex, can form in solution by translational and rotat ional diffusion in a field of force. Complexation criteria have been a ssessed based on the simultaneous alignment of three atom-atom contact s, as well as alternative criteria. The proteins are able to align one or two contacts at remarkably high rates, in fact, at rates approachi ng the diffusion-controlled limit for two spheres reactive over their entire surfaces. Three contacts may align, and hence the specific comp lex may dock, at rates on the order of 10(8) M(-1)s(-1), which is quit e representative of the experimental association rate constant for ET- competent complex(es). The formation of the specific complex is strong ly influenced by the favorable electrostatic interaction between these proteins. It is striking that a specific protein-protein complex can farm within one order of magnitude as fast as two spherical proteins c an touch at any orientation. It remains plausible that the high ET tun neling rate in this system can take place through a single highly favo rable specific complex using a single high efficiency pathway. Still t he contribution from a nonspecific set of complexes is not ruled out, particularly considering the marginal reproduction of the ionic streng th dependence in the formation of the xray complex.