Computer Simulation of Electron and Proton Transfer

电子和质子转移的计算机模拟

• 批准号: 6519301
• 负责人: ARIEH WARSHEL
• 金额: $ 20.31万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6519301
• 关键词: bacteriorhodopsins; bioenergetics; carbonate dehydratase; chemical kinetics; computer simulation; cytochrome oxidase; dielectric property; electron transport; gene mutation; hydrogen ions; hydrogen transporting ATP synthase; ionization; model design /development; molecular dynamics; oxidation reduction reaction; photosynthetic reaction centers; physical model; protein structure function; protonation; quantum chemistry; statistics /biometry; stereochemistry; structural biology; thermodynamics

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.

描述（由申请人提供）：电子传输（ET）和质子 易位（PTR）过程在生物能中起着至关重要的作用 转导。光合反应的结构研究的进步 中心（RCS）和最近阐明质子的结构 泵，例如细菌紫红质（BR）和细胞色素o氧酶，呈现 迈向详细的分子理解的激动人心的机会 生物ET和PTR过程。在过去的赠款期间，Warshel博士 开发，完善和检查的方法用于计算机的ET中的计算机模拟 蛋白质。这些方法用于研究主要事件的研究 细菌RCS和电子传输的氧化还原电势评估 蛋白质。最近，他还为 模拟蛋白质中的PTR并评估替代质子的可行性 传导途径。尽管他的方法有助于推进 了解细菌RC中的主要事件，关键基本问题 关于生物学ET仍未解决。就PTR而言，PI是 仍处于获得详细的过程的开始 结构功能相关性并获得定量分子 理解。他最近开发的方法使他处于独特的位置 能够帮助获得这样的理解。为了促进 生物ET和PTR领域的前沿，PI提出了以下 项目：（i）他将模拟细菌RCS中的PTR，细菌紫红素（BR）， 细胞chrcme C氧化酶和ATP合酶； （ii）他将完善并验证 通过执行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）他将继续对细菌RC的ET研究，同时着重于 （a）频谱的时间依赖性振荡，（b） 临界电离残基和（c）介电的时间依赖性 筛选和局部介电作用的性质； （iv）他将评估 生物捐赠者和受体氧化还原伙伴的重组能量； （v）他将利用Rhodopsm和 BR并模拟这些系统中主要事件的量子动力学。