COMPUTER SIMULATION OF ELECTRON TRANSFER REACTIONS

电子转移反应的计算机模拟

基本信息

批准号：
3297671
负责人：
ARIEH WARSHEL
金额：
$ 13.66万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-07-01 至 1997-06-30
项目状态：
已结题

项目摘要

Electron Transfer (ET) reactions play a major role in many biological and chemical processes. Early experimental and theoretical studies have identified the key factors in ET reactions and led to a qualitative picture using continuum solvent models. However, recent experiments have provided information at a level where the microscopic nature of the environment around donor and acceptor might be important. this is particularly relevant in studies of biological ET such as bacterial reaction centers (RC's) where the protein structure is known and the challenge is to reproduce experimental facts using this structure. The overall objective of this project is to advance the understanding of ET processes in biological and chemical systems to a microscopic level using computer simulation approaches. During the previous grant period we developed, examined and refined a wide range of simulation strategies for ET processes in proteins and solution, including a free energy perturbation/umbrella sampling method, semiclassical trajectory, dispersed polaron and density matrix approaches. These were applied to study ET processes in bacterial RC's and solution. Our studies and those of other groups demonstrated the usefulness of computer simulations. In particular, we were able to simulate ET in bacterial RC's and to examine different feasible mechanisms. In the current grant period we would like to move to a more quantitative level in the description of ET in proteins and solution. This will involve the following projects: (i) Further study of bacterial RC's. Earlier simulations yielded encouraging results but unique conclusions about the charge separation mechanism were not reached. Using longer simulations with improved long- range treatment while focussing on mutation effects is expected to give valuable information about the energetics of charge transfer states. (ii) Error range evaluation through extensive study of mutation effects on the redox potential of cytochromes and other proteins with mutants of known structure. The performance of several methods, including local reaction field augmented free energy perturbation, will be examined. (iii) Analysis of time resolved information about bacterial photosynthesis by various simulation methods. (iv) Exploration of the energetics of ET and proton transfer in the quinone sites. (v) Simulation of ET in Ru-cyt c to estimate the inherent dependence of the rate constant on the electronic coupling term, by factoring out the possible effect of protein fluctuations and reorganization energy. (vi) Simulation of ET in solution, using an explicit representation of donor and acceptor, trying to reproduce experimental results of well defined test cases.

电子转移（ET）反应在许多生物学和化学过程。早期的实验和理论研究确定了ET反应的关键因素，并导致了定性使用连续溶剂型号的图片。但是，最近的实验具有提供的信息以微观性质的级别围绕捐助者和受体的环境可能很重要。这是在生物学ET的研究（例如细菌）中特别相关反应中心（RC），其中蛋白质结构已知，挑战是使用此结构重现实验事实。这该项目的总体目标是提高对ET的理解生物学和化学系统中的过程达到微观水平计算机模拟方法。在上一个赠款期间我们开发，检查和完善了广泛的模拟策略蛋白质和溶液中的ET过程，包括自由能扰动/伞采样方法，半经典轨迹，分散的偏极和密度矩阵接近。这些被应用于研究细菌RC和溶液中的ET过程。我们的研究和那些在其他小组中，证明了计算机模拟的有用性。在特别是，我们能够在细菌RC中模拟ET并检查不同的可行机制。在当前的赠款期内，我们想要在蛋白质中的ET描述中移动到更定量的水平和解决方案。这将涉及以下项目：（i）进一步研究细菌RC。较早的模拟产生令人鼓舞的结果，但有关电荷分离的独特结论未达到机制。使用更长的模拟和改进的长期范围治疗重点是突变效应，预计将给出有关电荷转移状态的能量学的有价值信息。（ii）通过广泛研究突变效应的错误范围评估关于细胞色素和其他蛋白质的氧化还原潜力已知结构。包括本地的几种方法的性能将检查反应场增强自由能扰动。（iii）分析有关细菌的时间的分析通过各种模拟方法的光合作用。（iv）探索ET和质子转移的能量学喹酮站点。（v）在ru-cyt c中的ET模拟以估计固有的依赖性通过分解电子耦合项的速率常数蛋白质波动和重组能的可能影响。（vi）使用溶液中的ET模拟，使用明确表示捐助者和受体，试图再现井的实验结果定义的测试用例。