Computer Simulation of Electron and Proton Transfer

描述(申请人提供)：电子转移(ET)和质子 转位(PTR)过程在生物能源中起着至关重要的作用 转导。光合作用反应的结构研究进展 中心(RCS)和质子结构的最新阐明 泵，如细菌视紫红质(BR)和细胞色素C加氧酶，提供 向详细的分子理解迈进的令人兴奋的机会 生物ET和PTR过程。在过去的拨款期间，沃谢尔博士 开发、改进和检验了ET的计算机模拟方法 蛋白质。这些方法被用来研究 细菌RCS及其在评价电子传递氧化还原电位中的应用 蛋白质。最近，他还开发了一种有效的方法来治疗 蛋白质的PTRS模拟及替代质子的可行性评估 传导通路。尽管他的方法有助于推动 对细菌RCS中原发事件的理解，关键的基本问题 关于生物的ET仍然没有解决。就PTR而言，PI是 仍然处于获得详细信息的过程的开始 构效关系与定量分子的获得 理解。他最近开发的方法使他处于一个独特的位置 能够帮助获得这样的理解。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RCS中模拟PTR，细菌视紫红质(BR)， 细胞色素C氧化酶和三磷酸腺苷合成酶；(Ii)他将完善和验证 我们的PTR模拟中使用的简化自由能函数通过执行 明确定义的测试用例中的显式经验价键(EVB)模拟 (Iii)他将继续在细菌RCS中研究ET，同时专注于 (A)谱OFP的随时间变化的振荡，(B) 临界可电离残留物和(C)介质的时间依赖性 屏蔽和局部介电效应的性质；(Iv)他将评估 生物供体和受体氧化还原伙伴的重组能量； (V)他将利用最近可获得的视紫外结构和 Br并模拟这些系统中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.