Simulating proton transport at decorated surfaces and in cytochrome c oxidase by Q-HOP molecular dynamics simulations

通过 Q-HOP 分子动力学模拟模拟装饰表面和细胞色素 c 氧化酶中的质子传输

• 批准号: 85997781
• 负责人: Professor Dr. Volkhard Helms
• 金额: --
• 依托单位: Zentrum für Bioinformatik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/85997781?language=en
• 关键词: Simulating; proton; transport; decorated; surfaces

In biological cells, integral transmembrane proteins are responsible for maintaining a pH gradient across biological membranes. One very important system is cytochrome c oxidase (COX) that catalyzes the terminal step in cellular respiration, a four-electron transfer from cytochrome c to O2, in the inner membrane of mitochondria and many bacteria. Based on several X-ray structures of COX, two possible proton transfer pathways have been suggested that appear to be associated with different parts of the catalytic cycle. The coupling of proton transfers to the redox processes in COX is, however, largely unknown. We have previously developed an efficient molecular simulation method termed Q-HOP molecular dynamics (MD) that couples classical MD simulations for fixed titration states of a biomolecular system with stochastic proton hopping processes. Using this method, we were the first to characterize dynamic protonation equilibria of organic solutes in solution by unbiased MD simulations. Also, the method has been previously successfully applied to proton transfer processes in the green fluorescent protein and in aquaporin. Here, we propose to apply a refined version of QHOP MD to answer unresolved questions of surface-mediated proton transfer as well as of proton transport in cytochrome c oxidase.

在生物细胞中，完整的跨膜蛋白负责维持生物膜上的pH梯度。一个非常重要的系统是细胞色素c氧化酶（考克斯），它催化细胞呼吸的最终步骤，即线粒体和许多细菌内膜中从细胞色素c到O2的四电子转移。基于几个X-射线结构的考克斯，两种可能的质子转移途径已被提出，似乎是与不同的部分的催化循环。然而，在考克斯中质子转移与氧化还原过程的耦合在很大程度上是未知的。我们之前开发了一种高效的分子模拟方法，称为Q-HOP分子动力学（MD），该方法将生物分子系统固定滴定状态的经典MD模拟与随机质子跳跃过程结合起来。使用这种方法，我们是第一个表征动态质子化平衡的有机溶质在溶液中的无偏分子动力学模拟。此外，该方法已成功地应用于质子转移过程中的绿色荧光蛋白和水通道蛋白。在这里，我们建议应用一个改进版本的QHOP MD来回答未解决的问题，表面介导的质子转移，以及在细胞色素c氧化酶的质子运输。