Computer Simulations of Protein Structure and Dynamics

描述（由申请人提供）：本研究的目标是开发更准确的溶剂化蛋白质分子模拟方法，构建充分利用这些信息的多尺度动力学网络模型，以及将这些新的计算工具应用于结构生物学和分子生物物理学的前沿问题。这些问题包括： (a) 蛋白质-配体结合，热力学和动力学； (b) 表征天然状态下蛋白质折叠和功能转变的景观，重点是绘制折叠和结合途径的多样性及其相应的通量。这些项目将建立在当前拨款期间在开发最先进的蛋白质分子模拟方法以及最适合使用所有原子和多尺度动力学网络模型进行研究的前沿应用方面取得的实质性进展的基础上。

DESCRIPTION (provided by applicant): The goals of this research are the development of more accurate methods for molecular simulations of solvated proteins, the construction of multiscale kinetic network models which fully exploit this information, and the application of these new computational tools to forefront problems in structural biology and molecular biophysics. These problems include: (a) protein-ligand binding, both thermodynamics and kinetics; and (b) characterizing the landscapes for protein folding and functional transitions in the native state, with emphasis on mapping the diversity of pathways for folding and binding and their corresponding fluxes. These projects will build on the substantial progress made during the current grant period on the development of state-of-the-art methods for molecular simulations of proteins, and forefront applications which are best suited to investigation using all atom and multiscale kinetic network models.