Computer Simulations of Electron Transfer Proteins

关于电子转移蛋白最有趣的问题之一是蛋白质如何修饰电子 其氧化还原位点的转移特性。这些知识对于理解分子基础至关重要 各种代谢过程、涉及这些过程的疾病以及针对这些过程的药物设计 流程。总体目标是在分子水平上了解电子转移蛋白的特性。 重点是铁硫蛋白，它们是参与基本过程的普遍存在的蛋白质 例如呼吸作用、光合作用、生物合成和生物降解。我们的方法使用静电 势计算、分子动力学模拟、电子结构计算和序列 分析。我们的研究涵盖三个基本领域：（1）还原潜力（E），它决定了 电子转移的驱动力，（2）蛋白质重组能，它必须在如何发挥作用 蛋白质可以如此有效和快速地移动电子，并且（3）簇转换，这在 许多 Fe-S 蛋白的功能和形成。研究将主要集中在 2[4Fe-4S] 铁氧还蛋白和生物素上 合酶。具体目标是： 目标 1. 将确定由于 Fe-S 蛋白中的极性基团而导致的 E 差异的根源。我们的工作 模型是氧化还原位点的氢键主要通过氢键的静电影响 E 供体偶极子而不是通过电子扰动。 目标 2. 将确定 Fe-S 蛋白重组能的性质。我们的工作模式是 序列差异可以通过氢键影响重组能。 目标 3. 将确定 Fe-S 类似物和蛋白质中簇转化的机制。我们的 工作模型是自旋离域和氧化还原态很重要。

One of the most intriguing questions about electron transfer proteins is how the protein modifies the electron transfer properties of its redox site. This knowledge is crucial in understanding the molecular basis of a variety of metabolic processes, diseases involving these processes, and drug design targeting these processes. The overall goal is to understand the properties of electron transfer proteins at a molecular level. The focus is on the iron-sulfur proteins, which are ubiquitous proteins involved in fundamental processes such as respiration, photosynthesis, biosynthesis, and biodegradation. Our approach uses electrostatic potential calculations, molecular dynamics simulations, electronic structure calculations, and sequence analysis. Our studies cover three essential areas: (1) the reduction potentials (E),which determine the driving force for electron transfer, (2) the protein reorganization energy, which must play a role in how proteins can move electrons so efficiently and quickly, and (3) cluster conversion, which is important in the function and formation of many Fe-Sproteins. Studies will be mainly on the 2[4Fe-4S] ferredoxins and biotin synthase. The specific aimsare: Aim 1. The origins of differences in E due to polar groups in Fe-Sproteins will be determined. Our working model is that hydrogen bonds to the redox site affect E mainly by the electrostatics of the hydrogen bond donor dipole rather than by electronic perturbation. Aim 2. The nature of the reorganization energy of Fe-Sproteins will be determined. Our working model is that sequence differences can affect the reorganization energy via hydrogen bonds. Aim 3. The mechanisms of cluster conversion in Fe-S analogs and proteins will be determined . Our working model is that spin delocalization and redox state are important.