Complex I, NADH-ubiquinone oxidoreductase, is the first enzyme in the mitochondrial and bacterial aerobic respiratory chain. It pumps four protons through four transiently open pathways from the high pH, negative, N-side of the membrane to the positive, P-side driven by the exergonic transfer of electrons from NADH to a quinone. Three protons transfer through subunits descended from antiporters, while the fourth, E-channel is unique. The path through the E-channel is determined by a network analysis of hydrogen bonded pathways obtained by Monte Carlo sampling of protonation states, polar hydrogen orientation and water occupancy. Input coordinates are derived from molecular dynamics trajectories comparing oxidized, reduced (dihydro) and no menaquinone-8 (MQ). A complex proton transfer path from the N- to the P-side is found consisting of six clusters of highly connected hydrogen-bonded residues. The network connectivity depends on the presence of quinone and its redox state, supporting a role for this cofactor in coupling electron and proton transfers. The N-side is more organized with MQ-bound complex I facilitating proton entry, while the P-side is more connected in the apo-protein, facilitating proton exit. Subunit Nqo8 forms the core of the E channel; Nqo4 provides the N-side entry, Nqo7 and then Nqo10 join the pathway in the middle, while Nqo11 contributes to the P-side exit.

复合物I，NADH-泛醌氧化还原酶，是线粒体和细菌需氧呼吸链中的第一个酶。它通过从膜的高pH值，负N侧到正P侧的四个瞬态开放路径泵送四个质子，这些路径由电子从NADH到醌的能量转移而驱动。三个质子通过反向转运子的亚基转移，而第四个E通道是独特的。通过E通道的路径是通过对氢键键合路径的网络分析来确定的，该氢键合路径是通过质子态，极性氢取向和水占有率的蒙特卡洛采样获得的。输入坐标来自分子动力学轨迹，比较了氧化，还原（二氢）和无甲萘醌-8（MQ）。发现了从N侧到P侧的复杂质子传递路径，该路径由六簇高度连接的氢键合残基组成。网络连接性取决于醌的存在及其氧化还原状态，支持该辅因子在电子和质子传递耦合中的作用。N侧与MQ结合的复合物I更有条理，有助于质子进入，而P侧在脱辅基蛋白中的连接更多，有助于质子离开。Nqo8子单元构成E通道的核心；Nqo4提供N侧入口，Nqo7，然后Nqo10加入中间路径，而Nqo11则贡献给P侧出口。N侧与MQ结合的复合物I更有条理，有助于质子进入，而P侧在脱辅基蛋白中的连接更多，有助于质子离开。Nqo8子单元构成E通道的核心；Nqo4提供N侧入口，Nqo7然后Nqo10在中间加入路径，而Nqo11则贡献给P侧出口。N侧与MQ结合的复合物I更有条理，有助于质子进入，而P侧在脱辅基蛋白中的连接更多，有助于质子离开。Nqo8子单元构成E通道的核心；Nqo4提供N侧入口，Nqo7，然后Nqo10加入中间路径，而Nqo11则贡献给P侧出口。