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）：电子转移（ET）和质子 易位（PTR）过程在生物能源中发挥着至关重要的作用 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，例如细菌视紫红质 (bR) 和细胞色素 C 氧化酶，提供 深入了解分子细节的令人兴奋的机会 生物 ET 和 PTR 过程。在过去的资助期间，Warshel 博士 开发、完善和检验了 ET 的计算机模拟方法 蛋白质。这些方法用于对主要事件的研究 细菌 RC 和电子传递氧化还原电位的评估 蛋白质。最近，他还开发了一种有效的方法 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 的主要事件、关键的基本问题 关于生物ET仍然悬而未决。就 PTR 而言，PI 是 仍处于获取详细信息的过程的开始阶段 结构-功能关联并获得定量分子 理解。他最近开发的方法使他处于独特的地位 能够帮助获得这样的理解。为了推进 针对生物ET和PTR领域的前沿，PI提出以下建议 项目：(i) 他将在细菌 RC、细菌视紫红质 (bR)、 细胞色素c氧化酶和ATP合酶； (ii) 他将完善和验证 通过执行简化的 PTR 模拟中使用的自由能函数 在明确定义的测试用例中进行显式经验价键 (EVB) 模拟； (iii) 他将继续研究细菌 RC 中的 ET，同时重点关注 (a) P 频谱的时间相关振荡，(b) 的影响 临界电离残留物和 (c) 电介质的时间依赖性 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； (v) 他将利用最近发现的视紫红质结构 bR 并模拟这些系统中主要事件的量子动力学。