Theoretical and computational study of electron transport and redox-driven proton

这个计算项目的目标是促进对分子机制的理解 NADH脱氢酶（复合物I）-一种酶，是电子的进入点 需氧细胞呼吸系统中的运输链。已经确定酶 每个氧化的NADH的每2个电子泵4个质子，然而， 质子泵仍然是未知的。这项工作包括与一个领先的实验室合作， 他是该领域的专家，最近解决了酶的结构。 我们将测试的假设，电子隧穿沿着链的七个FeS集群在 酶的外周臂与长程构象变化偶联， 偶联质子转运在膜部分的酶;构象变化 推测是由一个半胱氨酸配体解离到末端N2 FeS诱导的 以其还原为中心; N2周围的局部结构松弛传递到 膜部分的酶，并诱导变构变化负责质子泵; 电子沿着沿着FeS团簇链隧穿的时间限制步骤提供了动力学门 这是构象驱动的质子泵机器运行所必需的。 该方法基于电子和质子的原子和量子力学模拟 传输，使用最先进的量子隧道计算和分子动力学 仿真。

The goal of this computational project is to advance understanding of the molecular mechanism of NADH dehydrogenase (Complex I) - an enzyme which is the entry point of the electron transport chain in the respiratory system of aerobic cells. It has been established that the enzyme pumps 4 protons per 2 electrons of each NADH oxidized, however the molecular mechanism of proton pumping remains unknown. The work includes collaboration with a leading experimental expert in the field, who recently solved the structure of the enzyme. We will test the hypothesis that electron tunneling along the chain of seven FeS clusters in the peripheral arm of the enzyme is coupled to a long-range conformational change which in turn is coupled to proton translocation in the membrane part of the enzyme; the conformational change is presumably induced by the dissociation of one of the cysteine ligands to the terminal N2 FeS center upon its reduction; the local structural relaxation around N2 is transmitted to the membrane part of the enzyme, and induces allosteric change responsible for proton pumping; the time-limiting step of electron tunneling along the chain of FeS clusters provides a kinetic gate necessary for operation of this conformation-driven proton pumping machine. The approach is based on atomistic and quantum mechanical simulations of electron and proton transport, using state-of-the art quantum tunneling calculations and molecular dynamics simulations.