Computer Simulation of Electron and Proton Transfer

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（RC）和系统的结构研究的进展，转移和/或泵质子，目前令人兴奋的机会，获得详细的了解生物ET和PTR过程的分子起源。在过去的资助期内，我们开发了计算机模拟生物ET的微观方法，并将其有效地应用于RC和相关系统的研究。在上一个资助期，我们开发了模拟蛋白质中PTR和离子转移的强大方法，并将其应用于关键系统的基础研究。我们的进展与最近在离子和质子通道结构解析方面的惊人进展相吻合，并增加了对生物PTR和离子选择性的微观性质的兴趣。在上一个资助期间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。为了建立静电概念的有效性，我们从我们早期修改的Marcus模型转移到简化的EVB方法，该方法应用于关键测试系统（碳酸酐酶和短杆菌肽）。我们还开始绘制几个关键生物系统中的PTR景观。因此，我们现在准备利用我们的进步，在现实的模拟研究PTR在生物系统中，我们有足够的结构信息。主要的研究项目包括：（i）利用简化的EVB方法研究细菌RCs和细菌视紫红质的PTR，以探索整个PTR过程，以及其与突变和构象变化的关系;（ii）通过改进的Marcus处理和简化的EVB方法研究考克斯的门控机制。(iii)探索ATP酶中质子梯度向ATP合成的转化。(iv)继续我们对细菌RC的研究。(v)继续蛋白质静电能的基础研究，（vi）继续我们对生物离子通道选择性的研究。

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.