Nonadiabatic Ring Polymer Molecular Dynamics for the Description of Biological Electron and Proton Transfer Processes

非绝热过程，如电子和质子耦合电子转移，在化学和生物能量转换反应中普遍存在。在现实的多维凝聚相系统中对这些过程的理论描述需要结合量子效应的分子动力学方法，包括非绝热跃迁、隧道和零点运动。本研究计划旨在发展并应用一种近似非绝热凝聚态量子分子动力学的新方法。环状聚合物分子动力学等基于路径积分的方法已被证明在凝聚相量子动力学中是成功的，并且对将这些方法扩展到非绝热状态有很大的兴趣。动力学约束的环状聚合物分子动力学方法在仅涉及两个电子态的非绝热给体-受体化学中表现出优异的性能，我建议将该方法推广到发生在多个势能表面上的非绝热动力学。Azurin是一个重要的生物电子和质子转移测试系统，具有丰富的实验数据。我将应用新方法详细描述azurin中的电子跳跃和电子跳跃耦合质子转移，这两种情况都涉及三个或更多势能面。我将讨论多步远程电子转移的详细机制，蛋白质和周围介质的影响，以及电子转移与质子运动的耦合。这项工作将受益于与加州理工学院实验组的密切合作，并将为模拟氧化还原活性蛋白质和蛋白质复合物中的生物电子、质子和质子偶联电子转移铺平道路，并将大量后续应用于核糖核苷酸还原酶、非血红素铁氧化还原酶、细胞色素P450和光系统II。

Nonadiabatic processes, such as electron and proton coupled electron transfers, are ubiquitous in chemical and biological energy conversion reactions. The theoretical description of these processes in realistic, multidimensional condensed phase systems requires molecular dynamics methods that incorporate quantum effects, including nonadiabatic transitions, tunneling and zero-point motion. This research proposal aims to develop and apply a novel method for approximate nonadiabatic quantum molecular dynamics in the condensed phase. Path integral-based approaches like ring polymer molecular dynamics have proved successful for condensed-phase quantum dynamics and there have been significant interest in extending these approaches to the nonadiabatic regime. The kinetically-constrained ring polymer molecular dynamics method has demonstrated excellent performance for nonadiabatic donor-acceptor chemistries, which involve only two electronic states, and I propose to generalize the method to nonadiabatic dynamics that takes place on multiple potential energy surfaces. Azurin is an important test system for biological electron and proton transfer with a wealth of available experimental data. I will apply the new method to describe in full atomistic detail electron hopping and electron hopping coupled with proton transfer in azurin, both of which involve three or more potential energy surfaces. I will address the detailed mechanism of multistep long-range electron transfer, the influence of the protein and the surrounding medium, and the coupling of the electron transfer with the proton motion. This work will benefit from close collaborations with experimental groups at Caltech and will pave the way to the simulation of biological electron, proton, and proton coupled electron transfers in redox active proteins and protein complexes with numerous follow-up applications to ribonucleotide reductase, non-heme iron oxidoreductases, cytochromes P450, and photosystem II.