Computer Simulation of Electron and Proton Transfer

描述(申请人提供)：电子转移(ET)和质子转移(PTR)在生物学中起着至关重要的作用。光合作用反应中心(RCs)以及传递和/或泵送质子的系统的结构研究的进展，为详细了解生物ET和PTR过程的分子起源提供了令人兴奋的机会。在过去的资助期间，我们开发了计算机模拟生物ET的微观方法，并将它们有效地应用于RCS及其相关系统的研究。在最后的资助期间，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。我们的进展与最近在离子和质子通道的结构阐明方面取得的惊人进展以及对生物PTR和离子选择性的微观性质的兴趣增加相吻合。上一次资助期间的研究支持了我们早期的观点，即蛋白质中的PTR是由转移的质子的静电能量控制的。为了确定静电思想的有效性，我们从早期修改的Marcus模型转移到简化的EVB方法，并将其应用于关键测试系统(碳酸酐酶和葛兰素)。我们还开始绘制几个关键生物系统的PTR图景。因此，我们现在已经准备好利用我们在具有足够结构信息的生物系统中PTR的现实模拟研究方面的进展。建议的主要项目是：(I)用简化的EVB方法研究细菌RCS和细菌视紫红质中的PTR，以探索整个PTR过程，以及它与突变和构象变化的关系；(Ii)用改进的Marcus‘s方法和简化的EVB方法研究COX的门控机制。(3)探索ATPase中质子梯度向ATP合成的转化。(4)继续研究细菌RCS。(V)继续对蛋白质中的静电能进行基础研究；(Vi)继续对生物离子通道的选择性进行研究。

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.