No abstract

extended-H[ckel approach to electronic coupling calculation is certainly dependent on its parameterization.The existence of multiple tunneling regimes also provides insight into several recent (and otherwise puzzling) experimental and theoretical observations in biological ET reaction kinetics. Winkler, Gray, and co-workers found that ET across protein-protein interfaces in protein crystals mediated by three water molecules is nearly as rapid as unimolecular ET is over the same distance (7). Canters and co-workers showed that water dimers between covalently cross-linked azurin complexes could substantially enhance the intermolecular ET kinetics (15). Similarly, Klinman and coworkers investigated the copper-to-copper ET over about 7 ) in the hydroxylating domain of peptidylglycine a-amidylating monooxygenase and found an unusually large electronic coupling mediated, apparently, by water rather than by the protein or substrate (17). Using Pathways-level analysis, Onuchic and co-workers found that water molecules mediate the dominant ET coupling routes between cytochrome c 2 and the photosynthetic reaction center (18). Cave and co-workers showed that water molecules between model D and A pairs substantially enhance intermolecular ET rates as well (19). All of these recent observations support our conclusion that a small number of structured water molecules interposed between the donor and the acceptor cofactors can substantially enhance ET rates.The influence of aqueous tunneling pathways on interprotein ET kinetics has remained a key open issue in biological ET for some time. Single-exponential decay models fail to describe water-mediated ET reactions properly. The existence of multiple tunneling mediating regimes identified above is evinced by a body of recent experimental and theoretical observations. Most importantly, the structured water coupling regime may provide an important mechanism to facilitate ET reactions in the critical near-contact distance range relevant to biological ET kinetics. We hypothesize that water may be a particularly strong tunneling mediator when it occupies a sterically constrained space between redox cofactors with strong organizing forces that favor constructively interfering coupling pathways. It will be particularly interesting to use both theory and experiment to explore how the watermediated coupling between proteins varies with protein-protein shape complementarity, surface charge and polarity, and dynamical fluctuations of the proteins and of the organized water at the interface. Chem. 88, 1321Chem. 88, (1984 . 106, 6647 (1997). 23. M. D. Newton, J. Electroanal. Chem. 438, 3 (1997). 24. S. Larsson, J. Phys.