Computer Simulations of Protein Structure and Dynamics

描述(申请人提供)：这项研究的目标是开发更准确的溶蛋白分子模拟方法，并将其应用于结构生物学和分子生物物理学的前沿问题。这项提议有三个具体的目标：(1)继续改进用于生物分子模拟的隐含溶剂的详细原子模型，(2)基于副本交换的新实现开发先进的生物分子模拟的采样方法，以及(3)将这些最先进的有效势和采样方法应用于结构生物学的关键问题：(A)与蛋白质的配体结合，(B)多肽结构系综和折叠路径的表征，以及(C)高分辨率的晶体与溶液环境对蛋白质的影响的模拟。这些项目将建立在当前赠款期间在开发最先进的有效潜力和用于蛋白质模拟的新颖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, 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.