Haapanen Outi, Djurabekova Amina, Sharma Vivek
Department of Physics, University of Helsinki, Helsinki, Finland.
Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
Front Chem. 2019 Apr 9;7:221. doi: 10.3389/fchem.2019.00221. eCollection 2019.
Respiratory complex I performs the reduction of quinone (Q) to quinol (QH) and pumps protons across the membrane. Structural data on complex I have provided spectacular insights into the electron and proton transfer paths, as well as into the long (30 Å) and unique substrate binding channel. However, due to missing structural information on Q binding modes, it remains unclear how Q reduction drives long range (20 nm) redox-coupled proton pumping in complex I. Here we applied multiscale computational approaches to study the dynamics and redox chemistry of Q and QH. Based on tens of microseconds of atomistic molecular dynamics (MD) simulations of bacterial and mitochondrial complex I, we find that the dynamics of Q is remarkably rapid and it diffuses from the N2 binding site to another stable site near the entrance of the Q channel in microseconds. Analysis of simulation trajectories also reveal the presence of yet another Q binding site 25-30 Å from the N2 center, which is in remarkable agreement with the electron density observed in recent cryo electron microscopy structure of complex I from . Quantum chemical computations on the two Q binding sites closer to the entrance of the Q tunnel reveal redox-coupled protonation reactions that may be important in driving the proton pump of complex I.
呼吸链复合体I负责将醌（Q）还原为氢醌（QH），并将质子泵过膜。关于复合体I的结构数据为电子和质子转移路径，以及长约30埃的独特底物结合通道提供了惊人的见解。然而，由于缺乏关于Q结合模式的结构信息，尚不清楚Q的还原如何驱动复合体I中长距离（约20纳米）的氧化还原偶联质子泵浦。在这里，我们应用多尺度计算方法来研究Q和QH的动力学及氧化还原化学。基于对细菌和线粒体复合体I长达数十微秒的原子分子动力学（MD）模拟，我们发现Q的动力学非常迅速，它在微秒内从N2结合位点扩散到Q通道入口附近的另一个稳定位点。对模拟轨迹的分析还揭示了在距N2中心25 - 30埃处存在另一个Q结合位点，这与最近在复合体I的冷冻电子显微镜结构中观察到的电子密度显著一致。对靠近Q隧道入口的两个Q结合位点进行的量子化学计算揭示了可能对驱动复合体I的质子泵起重要作用的氧化还原偶联质子化反应。
