Computer Simulations of Protein Structure and Dynamics

描述（由申请人提供）：本研究的目标是发展更精确的溶剂化蛋白质分子模拟方法，并将其应用于结构生物学和分子生物物理学的前沿问题。该提案有三个具体目标：(1)继续使用隐式溶剂改进生物分子模拟的详细原子模型；(2)基于副本交换的新实现开发先进的生物分子模拟采样方法；(3)将这些最先进的有效电位和采样方法应用于结构生物学的关键问题。(a)配体与蛋白质的结合，(b)多肽结构集合和折叠途径的表征，以及(c)高分辨率晶体与溶液环境对蛋白质影响的建模。这些项目将建立在当前资助期内取得的重大进展的基础上，这些进展包括开发最先进的有效电位和蛋白质模拟的新采样方法，以及最适合使用所有原子模型进行研究的前沿应用。

DESCRIPTION (provided by applicant): The goals of this research are the development of more accurate methods for molecular simulations of solvated proteins, and their application to forefront problems in structural biology and molecular biophysics. There are three specific aims of this proposal: (1) continue to improve detailed atomic models with implicit solvent for biomolecular simulations, (2) develop advanced sampling methods for biomolecular simulations based on novel implementations of replica exchange, and (3) apply these state-of-the-art effective potentials and sampling methods to key problems in structural biology: (a) ligand binding to proteins, (b) characterization of polypeptide structural ensembles and folding pathways, and (c) modeling of crystalline vs. solution environment effects on proteins at high resolution. These projects will build on the substantial progress made during the current grant period in the development of state-of-the-art effective potentials and novel sampling methods for protein simulations, and forefront applications which are best suited to investigation using all atom models.