Molecular modeling of charge transfer in heme-containing systems: a time-dependent view

血红蛋白是一大类金属蛋白，其中的血红素群赋予功能，包括携氧、氧还原、电子转移和其他过程。同时，这些蛋白质因其多样的生物学功能和广泛的丰度而成为研究最多的生物分子之一。一些系统包含少量的血红素基团，可能在其他氧化还原中心，而其他蛋白质包含许多血红素基团，以促进电荷在相对较大距离上的转移。含血红素蛋白中的电子转移已被提出遵循从闪烁共振上的顺序跳跃到纯相干转移的各种机制。本项目旨在为如何处理含血红素蛋白中的电子转移提供一个通用的方法，而不预先假设电子转移的具体模式，即不带任何偏见。为了证明待开发方案的普遍性，我们将研究具有少量血红素基团和相对较短电子转移过程的分子系统中的电子转移过程，即细胞色素bc1复合物，以及可能聚合并导致远程电子转移的蛋白质复合物，即OmcS蛋白。由于系统的大小，对过程的完全量子力学（QM）描述在数字上是令人望而却步的。同时，纯经典分子动力学（MD）模拟和基态量子力学/分子力学（QM/MM）描述由于这些表征的固有局限性而不够充分。因此，混合量子-经典方案是为了描述电子转移过程，我们的目标是开发具有明确定义的氧化还原中心的生物系统，在这些中心之间发生转移。具体来说，我们将采用一种混合程序，使用QM/MM MD方法来描述电子转移实体的原子水平动力学，并结合实际电子转移的粗粒度量子动力学描述，扩展了使用MD的早期方案，而不是现在提出的QM/MD模拟来描述分子水平。为了在含血红素的蛋白质中进行全面的电子转移模拟，计算生物物理学的方法必须取得根本性的进展。一个量子经典电子转移模拟的综合框架将是这个项目的第一个成果。第二个结果将包括bc1复合体和OmcS系统的完整模拟，这将最终使我们能够回答生物物理学中的基本问题，例如：bc1复合体中部分过程的功能如何在量子水平上促进整合到能量转换的整体机制中？波动和相干对电子通过OmcS纳米线的转移有哪些影响？

Hemeproteins represent a large class of metalloproteins, where the heme groups confers functionality, including oxygen-carrying, oxygen reduction, electron transfer, and other processes. At the same time, these proteins are among the most studied biomolecules because of their diverse biological functions and widespread abundance. Some systems contain a small number of heme groups, potentially among other redox centres, while other proteins include many heme groups to facilitate charge transfer over relatively large distances. The electron transfer in heme-containing proteins has been proposed to follow various mechanisms from sequential hopping over flickering resonances to purely coherent transfer. This project aims at providing a general recipe for how to treat electron transfer in heme-containing proteins with no prior assumptions on the specific mode of electron transfer, i.e., without any prejudice. To justify the generality of the to-be-developed protocols, we will study electron transfer processes in a molecular system with a few heme-groups and relatively short electron transfer processes, i.e., the cytochrome bc1 complex, and a protein complex that can potentially polymerize and lead to long-range electron transfers, i.e., the OmcS protein. Due to the size of the systems, a fully quantum mechanical (QM) description of the processes is numerically prohibitive. At the same time, purely classical molecular dynamics (MD) simulations and ground-state quantum mechanics/molecular mechanics (QM/MM) descriptions are not sufficient due to the inherent limitations of these representations. Thus, a mixed quantum-classical scheme is in order to delineate the electron transfer process that we aim to exploit for biological systems with clearly defined redox centres between which the transfer takes place. Specifically, we will employ a hybrid procedure using a QM/MM MD approach for the atomic-level dynamics of the electron transfer entities combined with a coarse-grained quantum dynamical description of the actual electron transfer extending an earlier scheme using MD instead of the now proposed QM/MD simulations for the molecular-level description. To carry out the full-scale electron transfer simulations in heme-containing proteins, fundamental advances have to be made in methods in computational biophysics. A comprehensive framework for quantum-classical electron transfer simulations will be the first outcome of this project. The second outcome will include complete simulations of the bc1 complex and the OmcS system that will ultimately allow us to answer fundamental questions in biophysics such as: How does the function of partial processes in the bc1 complex at the quantum level facilitate integration into the overall mechanism for energy conversion? Which effects do fluctuations and coherences have on the electron transfer through an OmcS nanowire?