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生物物理化学的前沿问题。有三个具体目标：(1)进一步开发用于生物分子模拟的隐式溶剂全原子有效势及其优化方法，(2)使用这些隐式溶剂模型来：探索蛋白质-配体结合特异性的分子基础，研究天然到熔融球状蛋白质的“熔化”转变，利用稀少的实验数据继续蛋白质结构确定工作，以及(3)通过将模拟信息与以新方式分析的核磁共振和单分子光学实验的信息相结合，更准确地、更长时间地表征蛋白质动力学。这些项目将建立在当前赠款期间所取得的进展的基础上，为蛋白质模拟和最适合使用所有原子模型进行研究的前沿应用开发“最先进”的有效潜力。

DESCRIPTION (provided by applicant): The goal of this research is the development of more accurate methods for molecular simulations of solvated proteins, and their application to forefront problems in structural biology and biophysical chemistry. There are three specific aims: (1) further develop implicit solvent all atom effective potentials for biomolecular simulations and methods for their optimization, (2) use these implicit solvent models to: explore the molecular basis for protein-ligand binding specificity, study the native to molten globule protein "melting" transition, continue work on protein structure determination using sparse experimental data, and (3) characterize protein dynamics more accurately and over longer times, by combining information from simulations with those from NMR and single molecule optical experiments analyzed in new ways. These projects will build on the progress made during the current grant period in the development of "state of the art" effective potentials for protein simulations and forefront applications which are best suited to investigation using all atom models.