Studies of redox-active sites in Photosystem II

光系统II（PSII）是一种多亚基氧化还原酶金属蛋白复合物， 在绿色植物叶绿体的类囊体膜和 蓝藻PSII建立ATP所需的膜pH梯度 合成，通过在氧气释放时氧化底物水来产生分子氧 复合物（OEC）和质体对苯二酚通过可逆还原和质子化 在QB生态位结合质体醌。我们的长期目标是澄清基本的 在OEC和QB氧化还原位点的催化方面，与其他金属酶相同， 包括活性位点氧化还原事件和配体自由基的作用以及 通过质子化或去质子化控制高氧化态金属氧中心的 机制等这些基本问题在代谢机制中普遍存在， 其它金属酶（例如，P-450、过氧化物酶和加氧酶）共同到不同 从细菌到人类的生物体类别，包括癌症，抗病毒药， 以及利用分子氧（或过氧化氢）作为底物的抗菌疗法。 我们使用高质量的量子力学密度泛函（DFT）方法， 量子力学/分子力学（QM/MM）混合方法来阐明 负责反应途径的氧化还原活性位点的结构/功能关系， 以及配体和除草剂结合的调节作用， 光谱学、诱变和动力学研究。新的计算方法， 包括描述自洽极化效应的严格方法 与生物分子中嵌入的辅基相关， 基于扩展X射线吸收精细结构（EXAFS）光谱的模拟 用于嵌入金属蛋白中的催化金属簇的结构细化， 结合亲和力的配体对接和评分以及QM/MM评价的组合 来造福计算机社区。

Photosystem II (PSII) is a multisubunit oxidoreductase metalloprotein complex found in the thylakoid membrane of green-plant chloroplasts and internal membranes of cyanobacteria. PSII establishes the membrane pH-gradient necessary for ATP synthesis, producing dioxygen by oxidation of substrate water at the oxygen evolving complex (OEC) and plastohydroquinone by reduction and protonation of reversibly bound plastoquinone at the QB niche. Our long-term goal is to clarify fundamental aspects of catalysis at the OEC and QB redox sites, common to other metalloenzymes, including the role of active site redox events and ligand radicals as well as the problem of controlling high oxidation state metal-oxygen centers by protonation or deprotonation mechanisms. These fundamental problems are ubiquitous in metabolic mechanisms of other metalloenzymes (e.g., P-450s, peroxidases and oxygenases) common to different classes of organisms from bacteria to humans, including drug targets in cancer, antiviral, and antibacterial therapies that utilize dioxygen (or hydrogen peroxide) as a substrate. We use high-quality quantum mechanical density functional (DFT) methods and quantum mechanical/molecular mechanics (QM/MM) hybrid methods to elucidate structure/function relations in redox active sites responsible for reaction pathways as well as the regulatory role of ligand and herbicide binding, making connections with spectroscopy, mutagenesis and kinetics studies. Novel computational methods, including rigorous approaches for the description of self-consistent polarization effects associated with prosthetic groups embedded in biological molecules, a new method based on simulations of extended X-ray absorption fine structure (EXAFS) spectroscopy for structural refinement of catalytic metal clusters embedded in metalloproteins, and the combination ligand docking and scoring and QM/MM evaluation of binding affinities aim to benefit the computational community, in general.