Topics in protein and RNA folding and dynamics

Devarajan (Dave) Thirumalai获得了化学学部化学理论、模型和计算方法项目的奖项，他开发了新的理论和计算方法，以了解蛋白质和核糖核酸（RNA）如何形成形状，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。它们通过采取特定的形状和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通过在极地轨道上行走来运输货物。这种运输是细胞正常运作所必需的。因此，化学和物理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门的生物物理学项目和物理部门的生命系统物理学项目对该奖项的贡献相同。除了学生和博士后助理之外，来自几所大学的本科生也参与了这些项目。为了实现上述广泛目标，Thirumalai博士在三个领域探讨了关键问题。(1)蛋白质折叠：为了发挥功能，蛋白质必须折叠成紧密的三维形状，这是由氨基酸的一级序列指定的。尽管基于不同实验的结论有所不同，但人们怀疑这一过程的初始步骤是链从扩展状态崩溃。为了解决这一重要的争议，Thirumalai博士将使用模型系统和蛋白质的完全原子细节模拟来解剖崩溃过程的本质。(2) RNA折叠：与蛋白质折叠不同，我们对RNA折叠知之甚少。这些由四个核苷酸构成的高电荷分子需要阳离子折叠。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。这个项目结合了分析理论和新颖的计算方法。(3)分子马达：运动蛋白、动力蛋白和肌凝蛋白是通过微管和肌动蛋白运输货物的马达，它们是极地轨道。许多漂亮的单分子实验表明，它们在这些轨道上手拉手地行走。这种运动的分子基础还没有被完全理解。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之间的耦合。此外，他和他的同事们探索了杠杆臂的设计，以探索他们在极地轨道上运动的稳健性。

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.