Topics in protein and RNA folding and dynamics

蛋白质和 RNA 折叠和动力学主题

基本信息

批准号：
1900093
负责人：
Devarajan Thirumalai
金额：
$ 123.97万
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：
2019
资助国家：
美国
起止时间：
2019-07-01 至 2023-06-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1900093&HistoricalAwards=false
关键词：
Topics protein RNA folding dynamics

项目摘要

Professor Devarajan (Dave) Thirumalai at the University of Texas Austin is supported by an award from the Chemical Theory, Models and Computational Methods Program in the Chemistry Division and the Molecular Biophysics Cluster in the Division of Molecular and Cellular Biosciences. Professor Thirumalai creates novel, theoretical, computational models in order to address outstanding questions in biologically-related research. For example, there are many proteins that do not adopt well-defined structures, these are referred to as Intrinsically Disordered Proteins (IDPs). IDPs behave like synthetic polymers but still control many biological functions. Professor Thirumalai uses computational models to predict the structure and reactions of IDPs with other IDPs as well as of IDPs with RNA (ribonucleic acid). The characteristics of RNA folding and interactions with unstructured proteins are of specific interest. Finally, the physical mechanisms by which molecular-sized motors, transport molecular "cargo" within cells are not well understood. Professor Thirumalai examines how these motors move and make their deliveries. In addition to the potential for broad impact of this research in biotechnology, Professor Thirumalai is devoted to the training of new generations of students in interdisciplinary research.In the last twenty years, it has become increasingly clear that nearly 40% of the proteome consists of the so-called low complexity IDPs, which are involved in a number of still unknown functions. A major goal of Professor Thirumalai's research is to develop reliable models that can quantitatively predict the structural and dynamical properties of IDPs. This first step is needed in order to understand how they interact with RNA and themselves in producing liquid droplets, which are recognized to be important, but whose properties are largely unknown. Another aspect of Professor Thirumalai's research deals with how RNA molecules fold, especially with the focus on the difficult problem of the mechanisms by which metal cations drive their folding. In addition, Thirumalai is keenly interested in uncovering the principles of RNA-RNA interactions. These structures also form droplets by themselves and in interactions with IDPs. Finally, two-headed molecular motors (Myosin, Dynein, and Kinesin) are largely responsible for transport of cargos in cells. They achieve this complex task by walking along actin and microtubules (MTs) in a preferred direction. One of Professor Thirumalai's major goals is to elucidate, using a combination of sophisticated theory and simulations, the structural basis by which the motors coordinate the two heads in a way such that one head steps forward while the other is bound to actin or MTs. Professor Thirumalai uses theoretical ideas to predict the outcomes of experiments, which include the distribution of motor velocities. These results are critically needed in order to redesign motors for synthetic purposes.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.

德克萨斯大学奥斯汀大学的Devarajan（Dave）Thirumalai教授得到了化学理论，模型和计算方法计划的奖项，而分子和细胞生物学分类的分子生物物理学集群则得到了化学理论，模型和计算方法计划。 Thirumalai教授创作了小说，理论，计算模型，以解决与生物学有关的研究中的杰出问题。例如，有许多蛋白质不采用明确定义的结构，这些蛋白质被称为本质上无序的蛋白质（IDP）。 IDP的行为就像合成聚合物一样，但仍然控制着许多生物学功能。 Thirumalai教授使用计算模型来预测IDP与其他IDP以及IDP与RNA（核糖核酸）的结构和反应。 RNA折叠的特征和与非结构化蛋白的相互作用具有特定的感兴趣。最后，尚不清楚分子大小的电动机，传输分子“货物”的物理机制。 Thirumalai教授研究了这些电动机如何移动和交付。除了在生物技术方面对这项研究产生广泛影响的潜力外，Thirumalai教授还致力于培训新一代的学生在跨学科研究中。在过去的二十年中，越来越明显的是，近40％的蛋白质组由所谓的低复杂性IDP组成，其中涉及许多仍然未知的功能。 Thirumalai教授的研究的主要目标是开发可靠的模型，以定量预测IDP的结构和动力学特性。为了了解它们如何与RNA相互作用，在产生液滴时，需要这一步，这被认为是重要的，但其特性在很大程度上是未知的。 Thirumalai教授的研究的另一个方面涉及RNA分子如何折叠，尤其是关注金属阳离子驱动其折叠的机制的困难问题。此外，Thirumalai对发现RNA-RNA相互作用的原理非常感兴趣。这些结构还可以自身形成液滴，并与IDP相互作用。最后，两头分子电动机（肌球蛋白，动力蛋白和驱动蛋白）在很大程度上负责细胞中钙的运输。他们通过沿肌动蛋白和微管（MTS）沿首选方向行走来实现这一复杂的任务。 Thirumalai教授的主要目标之一是使用复杂的理论和模拟的结合来阐明电动机以这种方式以一种方式来协调两个头部的结构基础，以使一个头向前迈进，而另一个则势必会肌动蛋白或MTS。 Thirumalai教授使用理论思想来预测实验的结果，其中包括运动速度的分布。这些结果至关重要，以重新设计用于合成目的的电机。该奖项反映了NSF的法定任务，并且使用基金会的知识分子优点和更广泛的影响标准，被认为值得通过评估来获得支持。