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

点击翻译按钮获取中文摘要

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.