COMPUTER SIMULATIONS OF ELECTRON TRANSFER PROTEINS

描述：关于电子最耐人寻味的问题之一 转移蛋白是蛋白质如何改变电子转移的。 给定类型的氧化还原位的属性。重要的是要知道，不仅是 这些蛋白质的结构，以及它们的结构来源 电子转移性质，以了解分子 疾病和药物设计的基础。这项研究的总体目标是 了解电子转移性质，特别是给体/受体 电子转移蛋白在分子水平上的能量相互作用 使用计算机模拟和其他理论方法。重点放在 铁硫蛋白，特别是单一的(Fe)Rubredoxin和 2(Fe-4S)(结构相关)铁氧还蛋白。这些无处不在的蛋白质 参与了基本的过程，如呼吸作用和 光合作用。此外，铁氧还蛋白与多种 更复杂的酶。然而，尽管数量迅速增加， 晶体结构，氧化还原电势的结构来源 蛋白质仍不清楚。前提是，它们主要是由于 极性主链、极性侧链和溶剂的静电效应。 特别是，观察到在还原时溶剂可及性的变化 在MD中，Rubredoxins的模拟可以解释一些令人困惑的数据 突变研究。此外，由于总的静电学是 来自蛋白质和溶剂的许多小贡献，而不是 几个关键的相互作用，这些相互竞争的影响往往很难 仅从结构化数据进行解析。Ichiye博士的方法主要是 基于对蛋白质的MD模拟，这对理解 这些复杂的现象，加上辅助性的电子 氧化还原位类似物的结构计算，从而给出了完整的图景 蛋白质的含量。前两个目标与Rubredoxins有关的具体目标 和铁氧还蛋白，并涉及到使用MD方法来预测 突变或同源蛋白中的氧化还原电位，然后寻找 它们的结构起源，从而提供了 实验和结构与氧化还原电位。第三个具体目标 涉及到使用MD模拟来检查核的贡献 极化对铁蛋白分子间电子转移的影响 可能是理解这两个氧化还原点的意义的关键，因为 在这种情况下，实验数据相对较少。这三个目标 将使我们对电子所涉及的蛋白质有更全面的了解 传输链以及它们如何确定流程中的能量流，例如 呼吸作用和光合作用。

DESCRIPTION: One of the most intriguing questions about the electron transfer proteins is how the protein modifies the electron transfer properties of a given type of redox site. It is crucial to know, not only the structure of these proteins, but also the structural origins of their electron transfer properties, to gain an understanding of the molecular basis of disease and drug design. The overall goal of this research is to understand the electron transfer properties particularly the donor/acceptor energetic interactions, of electron transfer proteins at a molecular level using computer simulations and other theoretical methods. The focus is on the iron-sulfur proteins, especially the single (Fe) rubredoxins and the 2(Fe-4S) (and structurally related) ferredoxins. These ubiquitous proteins are involved in fundamental processes such as respiration and photosynthesis. In addition, the ferrodoxins are homologous to a variety of more complex enzymes. However, despite the rapidly growing number of crystal structures, the structural origins of the redox potentials for these proteins remain unclear. The premise is that they are mainly due to the electrostatic effects of the polar backbone, polar side chains and solvent. In particular, the changes in solvent accessibility upon reduction observed in MD simulations of rubredoxins can explain some of the puzzling data from mutational studies. Moreover, since the total electrostatics is the sum of many small contributions from both the protein and the solvent, rather than a few key interactions, these competing effects are often difficult to resolve from structural data alone. The approach of Dr. Ichiye is mainly based on MD simulations of the protein, which are crucial to understanding these complex phenomena, in conjunction with come supplementary electronic structure calculations of redox site analogs, thus giving a complete picture of the protein. The first two aims specific aims concern the rubredoxins and the ferredoxins and involve using MD methods to predict difference in redox potentials in mutated or homologous proteins and then to look for their structural origins, thus providing the crucial link between experimental and structures and redox potentials. The third specific aim involves using MD simulations to examine the contribution of nuclear polarization to intermolecular electron transfer in the ferrodoxins, which may be key to understanding the significance of the two redox sites, since there relatively little experimental data in this case. These three aims will lead to a fuller understanding of the proteins involved in electron transport chains and how they determine energy flow in processes such as respiration and photosynthesis.