从头开始评估细胞色素c的氧化还原电位,Journal of Chemical Theory and Computation

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从头开始评估细胞色素c的氧化还原电位
Journal of Chemical Theory and Computation ( IF 5.7 ) Pub Date : 2021-01-17 , DOI: 10.1021/acs.jctc.0c00889
Cheng Cheng ₁ , Shigehiko Hayashi ₁

Affiliation

通过具有明确电子交换的氧化还原过程，可以实现代谢和生物合成的各种生化活性，从而为氧化还原酶提供高化学反应性。然而，对氧化还原过程的理论研究同时涉及到氧化还原金属中心的复杂电子变化以及周围蛋白质环境的构象重组，再加上电子变化，因此需要在计算上相互矛盾的方法，高度精确的量子化学计算和长期的研究分子动力学（MD）模拟，限制了对生物氧化还原过程的理化理解。在这里，我们从理论上通过混合分子模拟技术研究了细胞色素c的氧化还原过程，这样一来，人们就可以从头算量子化学理论上始终如一地处理氧化还原中心，并通过微秒级的长时间MD模拟来进行蛋白质重组。计算成功地评估了一个较大的绝对氧化还原电势，即4.34 eV，与实验值相比，仅具有0.03至0.34 eV的误差，而没有任何特定于问题的经验参数。通过长期的MD采样，揭示了蛋白质环境的大型且非线性重组，并确定了氧化还原电位的分子决定因素。目前的从头算方法极大地扩展了理论研究的适用性，使之具有更多的电子复杂的氧化还原中心，如多核过渡金属络合物的生物氧化还原系统。

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Ab Initio Evaluation of the Redox Potential of Cytochrome c

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.

更新日期：2021-02-09

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