Topics in Protein and RNA Folding and Dynamics

蛋白质和 RNA 折叠和动力学主题

• 批准号: 2320256
• 负责人: Devarajan Thirumalai
• 金额: $ 100万
• 依托单位: University of Texas at Austin
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2320256&HistoricalAwards=false
• 关键词: Topics; Protein; RNA; Folding; Dynamics

With support from the he Chemical Theory, Models and Computational Methods program in the Division of Chemistry (CHE) and the Molecular Biophysics program in the Division of Molecular and Cellular Biosciences (MCB), Professor Devarajan Thirumalai of the University of Texas at Austin will study the ways that proteins and RNA interact with each other to control a number of biophysical processes. In addition to DNA, which contains the blueprint of life, a myriad of cellular activities are determined by the diverse shapes and conformations that proteins and RNA adopt in different environments. Professor Thirumalai will develop new computational methods for simulating the molecular factors that determine droplet formation in disordered proteins and the mechanisms by which RNA molecules, previously thought to be merely passive carriers of informations, self-organize to form condensates. Professor Thirumalai will also work to develop both a theoretical framework and simulation methods to understand the molecular basis by which molecular motors, which carry cargo in cells, take multiple steps on polar tracks. These studies have the potential to provide a higher level of molecular understanding of complex biomacromolecular processes of relevance in biophysics. The research project will involve training students and postdoctoral fellows in interdisciplinary research areas, and will likely have broad impact in related areas in chemistry and the study of complex biochemical systems.In this project, the Thirumalai research team will create new coarse-grained models and computational tools to investigate (i) the conformational ensembles of intrinsically disordered proteins (IDPs), (ii) RNA folding, and (iii) the stepping mechanism of kinesin motors. The research team will employ multiscale simulations to investigate the effects of phosphorylation at specific sites on the assembly of fibril-forming IDPs along with the impact of crowded cellular environments on protein function. Regarding RNA folding, Professor Thirumalai will develop computational tools to account for multivalent ions ions, complimented by polyelectrolyte theories, and describe the thermodynamics and kinetics of folding of ribosomal RNAs. New methods to understand the mechanisms of cation-driven droplet formation and the associated dynamics in low complexity RNA sequences will likewise be devised. Finally, the stepping of kinesin on a microtubule (MT) will be simulated to address fundamental questions regarding the symmetry of the motor head motions: whether the detached kinesin motor passes the MT bound motor always on one side (symmetric walk) or alternates between two sides (asymmetric walk). In order to answer this and related questions, new models will be used to simulate multiple steps that kinesin takes on a MT. The software developed in these studies for exploring complex systems of biological importance will be made available for distribution.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在化学理论，模型和计算方法的支持下，在分子和细胞生物科学司（MCB）中，化学划分（CHE）和分子生物物理学计划（MCB），奥斯汀分校的Devarajan Thirumalai教授将研究蛋白质和RNA与每个人相互作用的方式，以控制一个数字的蛋白质和RNA。除了包含生命的蓝图的DNA外，无数的细胞活性还取决于蛋白质和RNA在不同环境中采用的各种形状和构象。 Thirumalai教授将开发新的计算方法，以模拟确定无序蛋白质中液滴形成的分子因子以及RNA分子（以前被认为仅仅是被动的信息载体，自组织形成冷凝物）的RNA分子的机制。 Thirumalai教授还将努力开发一种理论框架和仿真方法，以了解分子基础，该分子在细胞中携带货物的分子电机在极性轨道上采取多个步骤。 这些研究具有对生物物理学相关性复杂的生物分子过程的更高水平的分子理解。 The research project will involve training students and postdoctoral fellows in interdisciplinary research areas, and will likely have broad impact in related areas in chemistry and the study of complex biochemical systems.In this project, the Thirumalai research team will create new coarse-grained models and computational tools to investigate (i) the conformational ensembles of intrinsically disordered proteins (IDPs), (ii) RNA folding, and (iii) the stepping mechanism of动力机电机。 研究团队将采用多尺度模拟来研究特定位点上磷酸化对原纤维形成IDP组装的影响，以及拥挤的细胞环境对蛋白质功能的影响。关于RNA折叠，Thirumalai教授将开发计算工具来说明多价离子，并以多电解质理论的称赞，并描述核糖体RNA折叠的热力学和动力学。同样，也将设计理解阳离子驱动的液滴形成机制和低复杂性RNA序列中相关动力学的新方法。最后，将模拟驱动蛋白在微管（MT）上的踩踏以解决有关运动头运动的对称性的基本问题：分离的动力蛋白电动机是在一侧（对称性步行）（对称性步行）的MT绑定电动机还是在两个侧面（不对称步行）（不对称步行）。为了回答这个问题和相关的问题，新模型将用于模拟动力蛋白在MT上采用的多个步骤。这些研究中开发的用于探索生物学重要性的复杂系统的软件将用于分发。该奖项反映了NSF的法定任务，并使用基金会的知识分子优点和更广泛的影响审查标准，被认为值得通过评估来获得支持。