Computer Simulation of Electron and Proton Transfer

电子和质子转移的计算机模拟

• 批准号: 7264001
• 负责人: ARIEH WARSHEL
• 金额: $ 23.18万
• 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 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7264001
• 关键词: ATP Synthesis Pathway; ATP phosphohydrolase; Accounting; Anions; Bacteriochlorophylls; Bacteriorhodopsins; Biochemical; Biological; Biology; Carrier Proteins; Charge; Chemicals; Classification; Complex; Computer Simulation; Coupling; Cytochrome Peroxidase; Cytochromes; Dependence; Development; Devices; Electron Transport; Electrons; Electrostatics; Energy Transfer; Equation; Evaluation; Event; Free Energy; Generations; Gramicidin; Grant; Ion Channel; Ion Transport; Ions; Kinetics; Left; Link; Maps; Mechanics; Membrane; Membrane Proteins; Methods; Microscopic; Modeling; Molecular; Motion; Mutate; Mutation; Nature; Object Attachment; Operating System; Oxidation-Reduction; Pathway interactions; Pharmaceutical Preparations; Photosynthesis; Photosynthetic Reaction Centers; Play; Potassium Channel; Process; Progress Reports; Prostaglandin-Endoperoxide Synthase; Proteins; Proton Pump; Protons; Pump; Rate; Reaction; Relaxation; Resolution; Resources; Respiration; Role; Screening procedure; Simulate; Site; Solvents; Staging; Structure; System; Testing; Time; Water; base; carbonate dehydratase; cold temperature; cyclooxygenase 1; cytochrome c; cytochrome c oxidase; design; frontier; interest; models and simulation; pH gradient; prevent; quantum; simulation; tool; validation studies; virtual; water channel

DESCRIPTION (provided by applicant): Electron transfer (ET) and proton translocations (PTR) play a crucial role in biology. The advances in structural studies of photosynthetic reaction centers (RCs) and systems that transfer and/or pump protons, present the exciting opportunity of gaining a detailed understanding of the molecular origin of biological ET and PTR processes. In past grant periods, we developed microscopic approaches for computer simulation of biological ET and applied them effectively in studies of RCs and related systems. In the last grant period we developed powerful approaches for simulating PTR and ion transfer in proteins and applied these in fundamental studies of key systems. Our progress coincided with the recent spectacular progress in structure elucidation of ion and proton channels, and increased interest in the microscopic nature of biological PTR and ion selectivity. Studies during the last grant period supported our early view that PTR in proteins is controlled by the electrostatic energy of the transferred proton. To establish the validity of the electrostatic idea, we moved from our early modified Marcus' model to a simplified EVB approach which was applied to key test systems (carbonic anhydrase, and gramicidin). We also started to chart the PTR landscape in several key biological systems. Thus we are ready now to exploit our advances in realistic simulation studies of PTR in biological systems for which we have sufficient structural information. The main proposed projects are: (i) Studies of the PTR in bacterial RCs and bacteriorhodopsin using the simplified EVB approach to explore the overall PTR process, as well as its relationship to mutations and conformational changes, (ii) Studies of the gating mechanism of COX by the modified Marcus' treatment and by the simplified EVB. (iii) Exploring the conversion of the proton gradient to ATP synthesis in ATPase. (iv) Continuing our studies of the bacterial RCs. (v) Continuing fundamental studies of electrostatic energies in proteins and, (vi) continue our studies of the selectivity of biological ion channels.

描述（由申请人提供）：电子转移（ET）和质子易位（PTR）在生物学中起着至关重要的作用。光合反应中心（RCs）和传输和/或泵送质子的系统的结构研究的进展，为获得生物ET和PTR过程的分子起源的详细了解提供了令人兴奋的机会。在过去的资助期内，我们开发了生物ET计算机模拟的微观方法，并将其有效地应用于RCs和相关系统的研究中。在上一个资助期间，我们开发了强大的方法来模拟蛋白质中的PTR和离子转移，并将这些方法应用于关键系统的基础研究。我们的进展与近年来离子和质子通道结构解析的惊人进展相吻合，并增加了对生物PTR和离子选择性的微观性质的兴趣。上一个资助期的研究支持了我们早期的观点，即蛋白质中的PTR是由转移质子的静电能控制的。为了确立静电思想的有效性，我们从早期修改的Marcus模型转向简化的EVB方法，并将其应用于关键的测试系统（碳酸酐酶和革兰杀菌素）。我们也开始在几个关键的生物系统中绘制PTR景观图。因此，我们现在已经准备好利用我们在生物系统中PTR的现实模拟研究中的进展，我们有足够的结构信息。拟开展的主要项目有：(i)利用简化的EVB方法研究细菌RCs和细菌视紫红质中的PTR，探索PTR的整体过程及其与突变和构象变化的关系；（ii）利用改良的Marcus处理和简化的EVB研究COX的门控机制。（iii）探索ATP酶中质子梯度对ATP合成的转化。（iv）继续进行细菌红细胞的研究。（五）继续对蛋白质中的静电能进行基础研究；（六）继续研究生物离子通道的选择性。