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。它们提供了对生物分子活动机制的独特见解，有助于解释和整合实验信息，并越来越多地为新型生物分子和超分子系统的设计做出贡献。将在下一个项目期间进行的工作将增加此类研究的理论基础，贡献各种新的模拟工具，并应用模拟来探索重要的生物系统的活动。在理论领域，将继续努力提高自由能计算的严谨性，目标是为分子识别研究打造实用的新方法。在模拟工具领域，将创建算法和代码，以便能够更快地探索生物聚合物的构象，并能够在恒定pH下进行分子动力学模拟。计划探索蛋白激酶调节的生物物理学和烟碱型乙酰胆碱受体的作用，以探索具有挑战性的新应用。该项目将开发和应用使用计算机了解生物分子活动的方法。下一阶段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在下一个项目期开发的所有代码。对年轻科学家的培训将继续是国际和平协会小组的中心重点。在当前的项目期间，十多名小组成员转而担任终身教职。同样数量的本科生在进入研究生院之前参与了研究；这些学生中的许多人是根据他们的工作撰写的期刊文章的第一作者，还有几个人来自科学界代表性较低的群体。在下一个项目期，所有这些招聘活动都将继续进行。小组成员还将继续有机会在加州大学圣迭戈分校的常规课程和NSF理论生物物理中心提供的暑期学校任教。这有助于该小组成功地培训青年科学家从事学术和研究工作，也是科学界的一项宝贵的外展活动。

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.