Topics in protein and RNA folding and dynamics

蛋白质和 RNA 折叠和动力学主题

• 批准号: 1636424
• 负责人: Devarajan Thirumalai
• 金额: $ 89.49万
• 依托单位: University of Texas at Austin
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-19 至 2019-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1636424&HistoricalAwards=false
• 关键词: Topics; protein; RNA; folding; dynamics

Devarajan (Dave) Thirumalai is supported by an award from the Chemical Theory, Models and Computational Methods program in the Chemistry Division to develop novel theory and computational methods to understand how proteins and ribonucleic acids (RNA) get their shapes, and how these shapes affect their interaction with other substances. Proteins and RNA are among the most important molecules of life. They carry out all the functions in cells by adopting specific shapes and through mutual interactions. In a third project, Dr. Thirumalai uses modern theoretical and computational tools to decipher how molecular motors transport cargo by walking on polar tracks. Such transport is required for cells to function properly. Thus, fundamental principles of chemistry and physics are used to describe the molecular basis of the translation of cellular information, resulting in increased understanding of essential biological processes. The Biophysics program in the Division of Molecular and Cellular Biology and the Physics of Living Systems program in the Physics Division contribute equally to this award. In addition to students and postdoctoral associates, undergraduates from several universities contribute to these projects. In order to attain the broad goals outlined above, Dr. Thirumalai addresses key questions in three areas. (1) Protein Folding: In order to function, proteins must fold to a compact three-dimensional shape, which is specified by the primary sequence of amino acids. It is suspected that the initial step in this process is the collapse of the chain from an extended state although the conclusions based on different experiments vary. In order to resolve this important controversy, Dr. Thirumalai will use fully atomistically-detailed simulations of both model systems and proteins to dissect the nature of the collapse process. (2) RNA folding: In contrast to protein folding, little is known about RNA folding. These highly charged molecules, built from four nucleotides, require cations to fold. Thirumalai develops new models to describe how these cations interact with RNA to facilitate their folding. This project combines analytical theory with novel computational methods. (3) Molecular Motors: kinesin, dynein, and myosin are motors that transport cargo across microtubules and actin, which are polar tracks. Many beautiful single molecule experiments have shown that they walk hand-over-hand across these tracks. The molecular basis of this motion is not fully understood. Dr. Thirumalai develops new models to simulate their movements in order to illustrate the coupling between the internal dynamics and the motility. In addition, he and his coworkers explore the design of the lever arm to explore the robustness of their motions on the polar tracks.

Devarajan(Dave)Thirumalai得到了化学部化学理论、模型和计算方法项目的支持，该奖项旨在开发新的理论和计算方法，以了解蛋白质和核糖核酸(RNA)是如何形成形状的，以及这些形状如何影响它们与其他物质的相互作用。蛋白质和RNA是生命中最重要的分子。它们通过采用特定的形状并通过相互作用来执行细胞中的所有功能。在第三个项目中，Thirumalai博士使用现代理论和计算工具来破译分子马达如何在极地轨道上行走来运输货物。这样的运输是细胞正常运行所必需的。因此，化学和物理学的基本原理被用来描述细胞信息翻译的分子基础，从而增加了对基本生物过程的理解。分子和细胞生物学部的生物物理学项目和物理部的生命系统物理学项目对该奖项做出了同样的贡献。除了学生和博士后助理，来自几所大学的本科生也为这些项目做出了贡献。为了实现上述广泛目标，Thirumalai博士提出了三个方面的关键问题。(1)蛋白质折叠：为了发挥作用，蛋白质必须折叠成紧凑的三维形状，这是由氨基酸的初级序列指定的。人们怀疑，这个过程的第一步是链条从伸展状态崩溃，尽管基于不同实验的结论各不相同。为了解决这一重要争议，Thirumalai博士将使用对模型系统和蛋白质的完全原子化的详细模拟来剖析崩溃过程的本质。(2)RNA折叠：与蛋白质折叠相比，人们对RNA折叠知之甚少。这些由四个核苷酸组成的高电荷分子需要阳离子来折叠。Thirumalai开发了新的模型来描述这些阳离子如何与RNA相互作用以促进它们的折叠。该项目将分析理论与新的计算方法相结合。(3)分子马达：动蛋白、动力蛋白和肌球蛋白是通过微管和肌动蛋白运输货物的马达，微管和肌动蛋白是极轨迹。许多漂亮的单分子实验表明，它们手拉手地走过这些轨迹。这一动议的分子基础还没有完全被理解。Thirumalai博士开发了新的模型来模拟它们的运动，以说明内部动力学和运动性之间的耦合。此外，他和他的同事还探索了杠杆臂的设计，以探索它们在极地轨道上运动的健壮性。