Studies of redox-active sites in Photosystem II

光系统II(PSII)是一种发现的多亚单位氧化还原酶金属蛋白复合体 在绿色植物叶绿体的类囊体膜和绿色植物的内膜中 蓝藻。PSII建立了ATP所需的膜pH梯度 合成，通过底物水在放氧时氧化生产氧气 可逆地还原质子化的络合物(OEC)和塑料对苯二酚 在QB利基上结合了胞质苯二酚。我们的长期目标是澄清根本 其他金属酶共有的OEC和QB氧化还原位点的催化作用， 包括活性部位氧化还原事件和配基自由基的作用以及存在的问题 质子化或去质子化控制高氧化态金属氧中心 机械装置。这些基本问题在人体的代谢机制中普遍存在。 其他金属酶(如P-450、过氧化物酶和加氧酶) 从细菌到人类的各种生物体，包括癌症、抗病毒药物靶标， 以及利用氧气(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)方法和 量子力学/分子力学(QM/MM)混合方法阐明 氧化还原活性中心中与反应途径有关的结构/功能关系 以及配体和除草剂结合的调节作用，与 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 与嵌入在生物分子中的假体基团相关的一种新方法 基于扩展X射线吸收精细结构(EXAFS)谱的模拟 用于金属蛋白质中催化金属簇合物的结构优化，以及 结合配体对接评分及结合亲和力目标的QM/MM评价 以使计算社区总体受益。

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.