Computer Simulation of Electron and Proton Transfer

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DESCRIPTION (provided by applicant): Electron transfer (ET) and proton translocation (PTR) processes play a crucial role in biological energy transduction. The advances in structural studies of photosynthetic reaction centers (RCs) and the very recent elucidation of the structures of proton pumps, such as bacteriorhodopsin (bR) and cytochrome c oxydase, presents the exciting opportunity of progressing toward a detailed molecular understanding of biological ET and PTR processes. During the past grant periods, Dr. Warshel developed, refined and examined approaches for computer simulations of ET in proteins. These approaches were used in studies of the primary event of bacterial RCs and in evaluation of the redox potentials of electron transport proteins. Very recently, he has also developed an effective method for simulating PTRs in proteins and assessing the feasibility of alternative proton conduction pathways. Although his methods were helpful in advancing the understanding of the primary event in bacterial RCs, key fundamental questions about biological ET remain unresolved. As far as PTRs are concerned, the PI is still at the beginning of the processes of obtaining a detailed structure-function correlation and gaining a quantitative molecular understanding. His recently developed methods put him in a unique position of being able to help in obtaining such an understanding. In order to advance the frontiers of the fields of biological ET and PTR, the PI proposes the following projects: (i) He will simulate PTR in bacterial RCs, bacteriorhodopsin (bR), cytochrcme c oxidase and ATP synthase; (ii) He will refine and validate the simplified free energy functions used in our PTR simulations by performing explicit Empirical Valence Bond (EVB) simulations in well defined test cases; (iii) He will continue his studies of ET in bacterial RCs, while focusing on (a) the time dependent oscillations of the spectrum ofP, (b) the effect of critical ionizable residues and (c) the time dependence of the dielectric screening and the nature of the local dielectric effect; (iv) He will evaluate the reorganization energies of biological donor and acceptor redox partners; (v) He will exploit the recent availability of the structures of rhodopsm and bR and simulate the quantum dynamics of the primary event in these systems.