The oxidation of cytochrome f by the soluble cupredoxin plastocyanin is
a central reaction in the photosynthetic electron transfer chain of all oxygenic
organisms. Here, two different computational approaches are used to gain new
insights into the role of molecular recognition and protein-protein association
processes in this redox reaction. First, a comparative analysis of the computed
molecular electrostatic potentials of seven single and multiple point mutants
of spinach plastocyanin (D42N, E43K, E43N, E43Q/D44N, E59K/E60Q, E59K/E60Q/E43N,
Q88E) and the wt protein was carried out. The experimentally determined relative
rates (k(2)) for the set of plastocyanin mutants are found to correlate well
(r(2) = 0.90 - 0.97) with the computed measure of the similarity of the plastocyanin
electrostatic potentials. Second, the effects on the plastocyanin/cytochrome
f association rate of these mutations in the plastocyanin "eastern site" were
evaluated by simulating the association of the wild type and mutant plastocyanins
with cytochrome f by Brownian dynamics. Good agreement between the computed
and experimental relative rates (k(2)) (r(2) = 0.89 - 0.92) was achieved
for the plastocyanin mutants. The results obtained by applying both computational
techniques provide support for the fundamental role of the acidic residues
at the plastocyanin eastern site in the association with cytochrome f and
in the overall electron-transfer process.