Computer Simulation of Electron and Proton Transfer

电子和质子转移的计算机模拟

• 批准号: 7101021
• 负责人: ARIEH WARSHEL
• 金额: $ 23.88万
• 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/7101021
• 关键词: active transport; bacteriorhodopsins; bioenergetics; chemical kinetics; chemical models; computer simulation; cytochrome oxidase; dielectric property; electron transport; gene mutation; hydrogen ions; hydrogen transporting ATP synthase; ionic bond; ionization; membrane channels; model design /development; molecular dynamics; oxidation reduction reaction; photosynthetic reaction centers; protein structure function; protonation; structural biology

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）的结构研究和转移和/或泵质子的系统的进展，提供了对生物ET和PTR过程的分子起源的详细理解的令人兴奋的机会。在过去的赠款期间，我们开发了用于生物ET的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。在最后一个赠款期间，我们开发了模拟蛋白质中的PTR和离子转移的强大方法，并将其应用于关键系统的基本研究。我们的进步与最近阐明离子和质子通道结构的壮观进展相吻合，并增加了对生物PTR和离子选择性微观性质的兴趣。在最后一个赠款期间的研究支持了我们的早期观点，即蛋白质中的PTR受转移质子的静电能控制。为了建立静电想法的有效性，我们从早期修饰的MARCUS的模型转移到了简化的EVB方法，该方法应用于关键测试系统（碳酸酐酶和gramicidin）。我们还开始在几个关键的生物系统中绘制PTR景观。因此，我们现在准备在生物系统中对PTR进行现实的模拟研究中的进步，在这些研究中，我们拥有足够的结构信息。拟议的主要项目是：（i）使用简化的EVB方法研究细菌RC和细菌紫红素中PTR的研究，以探索整体PTR过程，以及其与突变和构象变化的关系，（ii）研究的研究机制研究通过改良的Marcus处理和简化的EVB进行COX。 （iii）探索质子梯度向ATPase中ATP合成的转化。 （iv）继续我们对细菌RCS的研究。 （v）蛋白质中静电能的持续基础研究和（vi）继续我们研究生物离子通道的选择性。