Computer Simulation of Electron and Proton Transfer

描述（由申请人提供）：电子转移（ET）和质子 蛋白质转运（PTR）过程在生物能源中起着至关重要的作用 转导光合反应结构研究进展 中心（RC）和最近对质子结构的阐明 泵，如细菌视紫红质（bR）和细胞色素c氧化酶，提出了 一个激动人心的机会， 生物ET和PTR过程。在过去的资助期间，Warshel博士 开发，完善和审查的方法，用于计算机模拟ET， proteins.这些方法被用于研究原发事件， 细菌RCs和电子传递的氧化还原电位的评价 proteins.最近，他还开发了一种有效的方法， 模拟蛋白质中的PTRs并评估替代质子的可行性 传导路径虽然他的方法有助于推进 了解细菌RC中的主要事件，关键的基本问题 关于生物外星人的问题还没有解决。就PTR而言，PI是 仍然在获得详细的 结构-功能关联，获得定量分子 认识他最近开发的方法使他处于一个独特的位置， 能够帮助我们获得这样的理解。为了推进 生物ET和PTR领域的前沿，PI提出以下建议 项目：（i）他将在细菌RC中模拟PTR，细菌视紫红质（bR）， 细胞色素c氧化酶和ATP合成酶;（ii）他将完善和验证 在我们的PTR模拟中使用的简化自由能函数， 明确定义的测试用例中的显式经验价键（EVB）模拟; (iii)他将继续研究细菌RCs中的ET，同时专注于 (a)P的光谱的时间依赖振荡，（B）的影响 临界可电离残留物和（c）电介质的时间依赖性 筛选和当地介电效应的性质;（四）他将评估 生物供体和受体氧化还原配偶体的重组能; (v)他将利用最近获得的视紫质结构， bR，并模拟这些系统中的初级事件的量子动力学。

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.