Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Av. da República, 2780-157 Oeiras, Portugal.
FEBS Lett. 2012 Mar 9;586(5):510-8. doi: 10.1016/j.febslet.2011.10.019. Epub 2011 Oct 19.
This article presents an overview of the simulation studies of the behaviour of multihaem cytochromes using theoretical/computational methodologies, with an emphasis on cytochrome c(3). It starts with the first studies using rigid molecules and continuum electrostatic models, where protonation and redox events were treated as independent. The gradual addition of physical details is then described, from the inclusion of proton isomerism, to the proper treatment of the thermodynamics of electron-proton coupling, to the explicit inclusion of the solvent and protein structural reorganization into the models, culminating with the method for molecular dynamics simulations at constant pH and reduction potential, where the solvation, conformational, protonation and redox features are all simulated in a fully integrated and coupled way. We end with a discussion of the strategies used to study the interaction between multihaem cytochromes, taking into account the further coupling effect introduced by the molecular association.
本文综述了使用理论/计算方法对多血红素细胞色素行为进行模拟研究的情况，重点介绍了细胞色素 c(3)。首先介绍了使用刚性分子和连续静电模型的早期研究，其中质子化和氧化还原事件被视为独立事件。然后逐步描述了物理细节的添加，从质子互变异构体的包含，到电子质子偶联热力学的正确处理，再到将溶剂和蛋白质结构重组明确纳入模型，最终采用在恒定 pH 和还原电势下进行分子动力学模拟的方法，其中对溶剂化、构象、质子化和氧化还原特性进行了完全集成和耦合的模拟。最后，我们讨论了用于研究多血红素细胞色素相互作用的策略，同时考虑了分子缔合引入的进一步耦合效应。
