Does internal water influence electron Tunneling in proteins?: Example of cytochrome c oxidase

In a recent study, the internal electron transfer in bovine heart cytochrome c oxidase (CcO) was examined using the tunneling currents method at the extended Huckel level of electronic structure. No internal water was present in the published structure of the enzyme, and none was taken into account in the calculations. Through computer simulation, we recently found an intriguing water hydrogen bond network in the vicinity of CcO catalytic site and in the region of electron tunneling. In this work, we reexamine the problem, with the focus on the possibility of the influence of water on electron transfer process. The calculations are carried out with the tunneling currents method implemented using more accurate ZINDO/S quantum chemical model. Results for the electron transfer from heme a to heme a, a key step in the function of the enzyme, are presented. With molecular dynamics simulations, we identify configurations in which the water molecules interfere with the tunneling pathway. The tunneling matrix element is evaluated by the flux theorem of the tunneling currents method, and is found to be 0.34 cm(-1) in the "dry" system and 1.38 cm(-1) in the "wet" system. The analysis of the tunneling flux indicates that the impact of water is localized on Phe(377) and spread to the methyl group and to His(376), both on the heme a, side of the ET pathway. The increase of the tunneling coupling by a factor of 4 in this case demonstrates that internal water in proteins can influence ET rate in proteins by as much as an order of magnitude. (c) 2004 Wiley Periodicals, Inc.