Topics in protein and RNA folding and dynamics

德克萨斯大学奥斯汀分校的Devarajan（Dave）Thirumalai教授获得了化学系化学理论，模型和计算方法项目以及分子和细胞生物科学系分子生物物理学集群的奖项。Thirumalai教授创建了新颖的理论计算模型，以解决生物学相关研究中的突出问题。例如，有许多蛋白质不采用明确定义的结构，这些蛋白质被称为内分泌紊乱蛋白（IDP）。内流离失所者的行为就像合成聚合物，但仍然控制着许多生物功能。 Thirumalai教授使用计算模型来预测IDPs与其他IDPs以及IDPs与RNA（核糖核酸）的结构和反应。RNA的折叠和与非结构化蛋白质的相互作用的特点是特别感兴趣的。最后，分子大小的马达在细胞内运输分子“货物”的物理机制还没有很好的理解。Thirumalai教授研究了这些马达是如何移动和交付的。 Thirumalai教授致力于培养跨学科研究的新一代学生。在过去的二十年里，人们越来越清楚地发现，近40%的蛋白质组由所谓的低复杂性IDP组成，它们参与了许多未知的功能。Thirumalai教授研究的一个主要目标是开发可靠的模型，可以定量预测IDP的结构和动力学特性。这第一步是必要的，以了解它们如何与RNA相互作用，并在产生液滴，这被认为是重要的，但其性质在很大程度上是未知的。Thirumalai教授研究的另一个方面涉及RNA分子如何折叠，特别是关注金属阳离子驱动其折叠的机制这一难题。此外，Thirumalai对揭示RNA-RNA相互作用的原理非常感兴趣。 这些结构本身也形成液滴，并与国内流离失所者相互作用。最后，双头分子马达（肌球蛋白、动力蛋白和驱动蛋白）主要负责细胞内货物的运输。它们通过沿着肌动蛋白和微管（MT）在优选方向上行走来完成这一复杂任务。Thirumalai教授的主要目标之一是使用复杂的理论和模拟相结合来阐明电机协调两个头部的结构基础，使得一个头部向前移动，而另一个头部则与肌动蛋白或MT绑定。Thirumalai教授使用理论思想来预测实验结果，其中包括运动速度的分布。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.