Topics in protein and RNA folding and dynamics

Devarajan（Dave）Thirumalai获得了化学部化学理论，模型和计算方法计划的奖项，以开发新的理论和计算方法来了解蛋白质和核糖核酸（RNA）如何获得它们的形状，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之一。它们通过采用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工作所必需的。 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。 分子和细胞生物学系的生物物理学课程以及物理学系的生命系统物理学课程对该奖项做出了同样的贡献。 除了学生和博士后研究员之外，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博士在三个领域解决了关键问题。(1)蛋白质折叠：为了发挥功能，蛋白质必须折叠成紧凑的三维形状，这是由氨基酸的一级序列指定的。有人怀疑，在这个过程中的第一步是从一个扩展状态的链崩溃，虽然根据不同的实验得出的结论各不相同。为了解决这个重要的争议，Thirumalai博士将使用模型系统和蛋白质的完全原子详细的模拟来剖析崩溃过程的性质。(2)RNA折叠：与蛋白质折叠相反，人们对RNA折叠知之甚少。这些高度带电的分子由四个核苷酸组成，需要阳离子才能折叠。Thirumalai开发了新的模型来描述这些阳离子如何与RNA相互作用以促进其折叠。 该项目将分析理论与新颖的计算方法相结合。(3)分子马达：驱动蛋白、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性轨道。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完全弄清楚。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鲁棒性。

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.