Theory of Biomolecular Structure and Dynamics

分子动力学模拟研究在分子生物物理学中发挥着越来越重要的作用。 他们提供了独特的见解生物分子活性的机制，在实验信息的解释和整合援助，并-越来越多的-有助于设计新的生物分子和超分子系统。 在下一个项目期间将开展的工作将为这些研究奠定理论基础，提供各种新的模拟工具，并应用模拟来探测重要生物系统的活动。 在理论领域，正在进行的努力，以提高自由能计算的严谨性将扩大与锻造实用的新方法的分子识别研究的目标。 在模拟工具方面，将开发算法和代码，以便更快地探索生物聚合物的构象，并在恒定pH值下进行分子动力学模拟。计划开发新的应用，以探索蛋白激酶调节和烟碱乙酰胆碱受体的作用的生物物理学。本项目将开发和应用使用计算机了解生物分子活性的方法。 下一个时期将出现的计算工具将包括对几个广泛使用的软件包的增强，以允许在恒定pH值下进行分子动力学模拟，通过加速分子动力学增强采样，以及更准确地计算自由能。 PI将继续尽可能自由地分发下一个项目期间开发的所有代码。 青年科学家的培训将继续是PI小组的中心重点。 在本项目期间，有十几名小组成员进入了终身教职。 类似数量的本科生在进入研究生院之前参加了研究;这些学生中的许多人是基于他们工作的期刊文章的第一作者，还有一些人来自科学界代表性不足的群体。 在下一个项目期间，所有这些征聘活动将继续进行。 小组成员还将继续有机会在UCSD的常规课程和NSF理论生物物理中心提供的暑期学校任教。 这有助于PI小组成功地为学术和研究事业培训年轻科学家，也是对科学界的一项宝贵的外联活动。

Molecular dynamics simulation studies play an ever-increasing role in molecular biophysics. They provide unique insights into the mechanisms of biomolecular activity, aid in the interpretation and integration of experimental information, and - increasingly - contribute to the design of novel biomolecular and supramolecular systems. The work that will be conducted during the next project period will add to the theoretical foundations for such studies, contribute a variety of new simulation tools, and apply simulations to probe the activity of important biological systems. In the theory area, ongoing efforts to improve the rigor of free energy calculations will be extended with the goal of forging practical new methods for the study of molecular recognition. In the area of simulation tools, algorithms and codes will be created to allow faster exploration of the conformations of biopolymers and to enable molecular dynamics simulations at constant pH. Challenging new applications are planned to explore the biophysics of protein kinase regulation and the action of nicotinic acetylcholine receptors.This project will develop and apply methods for using computers to understand the activity of biological molecules. Computational tools that will emerge during the next period will include enhancements to several widely used software packages to allow molecular dynamics simulations at constant pH, enhanced sampling via accelerated molecular dynamics, and more accurate calculations of free energy. The PI will continue to distribute all codes developed in the next project period as freely as possible. The training of young scientists will continue to be a central focus of the PI's group. More than a dozen group members moved on to tenure-track faculty positions in the current project period. A similar number of undergraduates participated in research prior to going on to graduate school; many of these students are first authors of journal articles based on their work, and several are from underrepresented groups in science. During the next project period, all of these recruitment activities will continue. Group members will also continue to have the opportunity to teach in regular courses at UCSD and in summer schools offered by the NSF Center for Theoretical Biological Physics. This contributes to the success of the PI's group in training young scientists for academic and research careers, and also represents a valuable outreach activity to the scientific community.