Integrated Quantum, Moleucles, Solvatoin, Charge State Simulations of Proteins

蛋白质的功能和反应性是其原子和电子结构、动力学和辅因子的产物。这项研究的目标是超越一些反应如何发生的定量描述，为什么它会发生，在原子或官能团的水平和原则方面的事件的理解。该项目的核心主题是能量转换或耦合的概念，既作为一个总体的解释原则，也作为一个调查工具。蛋白质内部和外部Stark测量的新测量和分析（将电能转换为蛋白质的变化） 光谱跃迁能量）将探测蛋白质辅因子的环境， 这些蛋白调节辅因子功能和反应性的机制。高分辨率光谱分析将用于研究溶剂和蛋白质动力学与蛋白质能量景观之间的关系（溶剂和蛋白质波动的能量如何转换为其他激活和功能模式），使用最近集成的模拟和理论工具。项目#4的第一个目标是开发一套连贯的模拟技术， 辅因子电子结构，通过模拟蛋白质运动，通过长时间尺度的溶剂，静电和电荷转移效应，结合量子化学计算，经典动力学和有限差分Poisson-Boltzmann方法。项目#4的第二个目标是将这套模拟技术应用于特定问题：蛋白质和溶剂对血红素性质的影响，蛋白质动力学的定量表征以及蛋白质内部静电场的影响。

A protein's function and reactivity is the product of its atomic and electronic structure, its dynamics, and its cofactors. The goal of this research is to go beyond quantitative descriptions of how some reaction occurs to why it occurs, to an understanding of the events, at both the level of atoms or functional groups and in terms of principles. The nucleating theme of the program project is the concept of energy transduction or coupling, both as an overarching explanatory principle, and as an investigative tool. Novel measurements and analysis of internal and external Stark measurements on proteins (transduction of electrical energy into changes in spectral transition energies) will probe the environment of protein cofactors, and the mechanisms by which these proteins modulate cofactor function and reactivity. Analysis of high resolution spectroscopy will be used to study the relationship between solvent and protein dynamics and the protein's energy landscape (How the energy of solvent and protein fluctuations is transduced into other activated and functional modes), using recently integrated simulation and theoretical tools. The first aim of project # 4 is to develop a coherent suite of simulation technologies that can span the range from quantum chemical calculations of cofactor electronic structure, via simulation of protein motions, through to long time scale solvent, electrostatic and charge transfer effects, by combining quantum chemical calculations, classical dynamics and finite difference Poisson-Boltzmann methods. The second aim of project # 4 is to apply this suite of simulation technologies to specific problems: The effect of protein and solvent on heme properties, quantitative characterization of protein dynamics, and the effect of internal electrostatic fields of proteins.