Department of Inorganic Chemistry, Budapest University of Technology and Economics, H-1111, Budapest, Szent Gellért tér 4., Hungary.
MTA-ELTE Protein Modelling Research Group, H-1117, Budapest, Pázmány Péter st. 1/A, Hungary.
Chemistry. 2018 Apr 6;24(20):5350-5358. doi: 10.1002/chem.201704867. Epub 2018 Feb 6.
Ligand binding by proteins is among the most fundamental processes in nature. Among these processes the binding of small gas molecules, such as O , CO and NO to heme proteins has traditionally received vivid interest, which was further boosted by their recently recognized significant role in gas sensing in the body. At the heart of the binding of these ligands to the heme group is the spinforbidden reaction between high-spin iron(II) and the ligand yielding a low-spin adduct. We use computational means to address the complete mechanism of CO and NO binding by myoglobin. Considering that it involves several steps occurring on different time scales, molecular dynamics simulations were performed to address the diffusion of the ligand through the enzyme, and DFT calculations in combination with statistical rate calculation to investigate the spin-forbidden reaction. The calculations yielded rate constants in qualitative agreement with experiments and revealed that the bottleneck of NO and CO binding is different; for NO, diffusion was found to be rate-limiting, whereas for CO, the spin-forbidden step is the slowest.
蛋白质与配体的结合是自然界中最基本的过程之一。在这些过程中，小分子气体（如 O 、CO 和 NO）与血红素蛋白的结合一直受到广泛关注，而近年来这些气体在体内气体感应中的重要作用进一步推动了这一研究。这些配体与血红素基团结合的核心是高自旋铁（II）与配体之间的自旋禁阻反应，生成低自旋加合物。我们使用计算手段来研究肌红蛋白与 CO 和 NO 的结合的完整机制。由于它涉及到几个发生在不同时间尺度上的步骤，我们进行了分子动力学模拟来研究配体通过酶的扩散，以及 DFT 计算结合统计速率计算来研究自旋禁阻反应。计算得到的速率常数与实验定性一致，并表明 NO 和 CO 结合的瓶颈是不同的；对于 NO，扩散被发现是限速步骤，而对于 CO，自旋禁阻步骤是最慢的。
