Ab Initio Evaluation of the Redox Potential of Cytochrome c
Ab Initio Evaluation of the Redox Potential of Cytochrome c
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DOI：
10.1021/acs.jctc.0c00889
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发表时间：
2021-01-17
影响因子：
5.5
通讯作者：
Hayashi, Shigehiko
中科院分区：
文献类型：
--
作者：
Cheng, Cheng;Hayashi, Shigehiko
代谢和生物合成的各种生物化学活动是通过具有明确电子交换的氧化还原过程来完成的，这为氧化还原酶提供了高化学反应性。然而，氧化还原过程的理论研究，同时涉及一个复杂的电子变化在氧化还原金属中心和周围的蛋白质环境的构象重组耦合到电子变化，需要计算冲突的方法，高度精确的量子化学计算，和长时间的分子动力学（MD）模拟，限制了物理化学的理解生物氧化还原过程。在这里，我们从理论上研究了细胞色素c的氧化还原过程的混合分子模拟技术，这使得一个始终治疗氧化还原中心的从头算量子化学水平的理论和蛋白质重组与长时间的MD模拟微秒的时间尺度。计算成功地评估了一个大的绝对氧化还原电位，4.34 eV，只有0.03至0.34 eV的误差，没有任何问题的具体经验参数的实验。通过长时间的MD采样，揭示了蛋白质环境的大的和非线性的重组，并确定了氧化还原电位的分子决定因素。目前的从头算方法显着扩大了适用性的理论研究的生物氧化还原系统，更复杂的电子氧化还原中心，如多核过渡金属配合物。
Various biochemical activities of metabolism and biosynthesis are fulfilled by redox processes with explicit electron exchange, which furnish redox enzymes with high chemical reactivity. However, theoretical investigation of a redox process, which simultaneously involves a complex electronic change at a redox metal center and conformational reorganization of the surrounding protein environment coupled to the electronic change, requires computationally conflicting approaches, highly accurate quantum chemical calculations, and long-time molecular dynamics (MD) simulations, limiting the physicochemical understanding of biological redox processes. Here, we theoretically examined a redox process of cytochrome c by means of a hybrid molecular simulation technique, which enables one to consistently treat the redox center at the ab initio quantum chemistry level of theory and the protein reorganization with long-time MD simulations on the microsecond timescale. The calculations successfully evaluated a large absolute redox potential, 4.34 eV, with errors of only 0.03 to 0.34 eV to the experimental ones without any problem-specific empirical parameters. Through the long-time MD sampling, large and nonlinear reorganization of the protein environment was unveiled and the molecular determinants for the redox potential were identified. The present ab initio approach significantly expands the applicability of theoretical investigation to biological redox systems with more electronically complicated redox centers such as polynuclear transition metal complexes.