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:
- 金额:$ 123.97万
- 依托单位:
- 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:
- 关键词:
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分校的Devarajan (Dave) Thirumalai教授获得了化学学部化学理论、模型和计算方法项目以及分子和细胞生物科学部分子生物物理集群的奖项。Thirumalai教授创建了新颖的理论计算模型,以解决生物相关研究中的突出问题。例如,有许多蛋白质不采用定义明确的结构,这些被称为内在无序蛋白质(IDPs)。IDPs的行为类似于合成聚合物,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折叠的特点和与非结构蛋白的相互作用是特别感兴趣的。最后,分子大小的马达在细胞内运输分子“货物”的物理机制尚不清楚。Thirumalai教授研究了这些马达是如何运动和输送的。除了这项研究可能对生物技术产生广泛影响外,Thirumalai教授还致力于培养新一代跨学科研究的学生。在过去的二十年中,越来越清楚的是,近40%的蛋白质组由所谓的低复杂性IDPs组成,它们涉及许多未知的功能。Thirumalai教授研究的一个主要目标是开发可靠的模型,可以定量预测国内流离失所者的结构和动态特性。为了了解它们如何与RNA和自身相互作用以产生液滴,这是必要的第一步,液滴被认为是重要的,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。这些结构本身也会形成液滴,并与IDPs相互作用。最后,双头分子马达(肌凝蛋白、动力蛋白和运动蛋白)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(MTs)沿着首选方向行走来完成这项复杂的任务。Thirumalai教授的主要目标之一是通过复杂的理论和模拟相结合,阐明电机协调两个头部的结构基础,使一个头部向前迈步,而另一个头部被约束在动作或mt上。Thirumalai教授使用理论思想来预测实验结果,其中包括电机速度的分布。为了重新设计用于合成目的的电机,这些结果是非常需要的。该奖项反映了美国国家科学基金会的法定使命,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。
项目成果
期刊论文数量(16)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Step-Wise Hydration of Magnesium by Four Water Molecules Precedes Phosphate Release in a Myosin Motor.
在肌球蛋白运动中磷酸盐释放之前,四个水分子对镁的逐步水合。
- DOI:10.1021/acs.jpcb.0c10004
- 发表时间:2021
- 期刊:
- 影响因子:0
- 作者:Mugnai,MauroLorenzo;Thirumalai,D
- 通讯作者:Thirumalai,D
Charge Density of Cation Determines Inner versus Outer Shell Coordination to Phosphate in RNA
阳离子的电荷密度决定了 RNA 中磷酸根的内壳与外壳的配位
- DOI:10.1021/acs.jpcb.0c02371
- 发表时间:2020
- 期刊:
- 影响因子:0
- 作者:Nguyen, Hung T.;Thirumalai, D.
- 通讯作者:Thirumalai, D.
Theory and simulations for RNA folding in mixtures of monovalent and divalent cations
- DOI:10.1073/pnas.1911632116
- 发表时间:2019-09
- 期刊:
- 影响因子:0
- 作者:H. T. Nguyen;N. Hori;D. Thirumalai
- 通讯作者:H. T. Nguyen;N. Hori;D. Thirumalai
Molecular Transfer Model for pH Effects on Intrinsically Disordered Proteins: Theory and Applications
pH 对本质无序蛋白质影响的分子转移模型:理论与应用
- DOI:10.1021/acs.jctc.0c01316
- 发表时间:2021
- 期刊:
- 影响因子:5.5
- 作者:Mugnai, Mauro Lorenzo;Thirumalai, D.
- 通讯作者:Thirumalai, D.
How kinesin waits for ATP affects the nucleotide and load dependence of the stepping kinetics
驱动蛋白等待 ATP 如何影响步进动力学的核苷酸和负载依赖性
- DOI:10.1073/pnas.1913650116
- 发表时间:2019
- 期刊:
- 影响因子:0
- 作者:Takaki, Ryota;Mugnai, Mauro L.;Goldtzvik, Yonathan;Thirumalai, D.
- 通讯作者:Thirumalai, D.
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Devarajan Thirumalai其他文献
Hydration of Magnesium is Required for Myosin VI Phosphate Release
- DOI:
10.1016/j.bpj.2017.11.1788 - 发表时间:
2018-02-02 - 期刊:
- 影响因子:
- 作者:
Mauro L. Mugnai;Devarajan Thirumalai - 通讯作者:
Devarajan Thirumalai
TMAO and Solvent Exposed RNA Bases Stabilizes Unfolded State via Hydrogen Bonding
- DOI:
10.1016/j.bpj.2008.12.3009 - 发表时间:
2009-02-01 - 期刊:
- 影响因子:
- 作者:
Samuel Cho;Devarajan Thirumalai - 通讯作者:
Devarajan Thirumalai
Crowding Induced Conformational Switch
- DOI:
10.1016/j.bpj.2010.12.240 - 发表时间:
2011-02-02 - 期刊:
- 影响因子:
- 作者:
Devarajan Thirumalai - 通讯作者:
Devarajan Thirumalai
Searching, Stepping, and Stomping: What Polymer Theory can teach us about the Molecular Motor Myosin V
- DOI:
10.1016/j.bpj.2012.11.3553 - 发表时间:
2013-01-29 - 期刊:
- 影响因子:
- 作者:
Michael Hinczewski;Riina Tehver;Devarajan Thirumalai - 通讯作者:
Devarajan Thirumalai
Impact of TMAO on the preQ1 RNA Riboswitch Studied using Molecular Dynamics Simulations
- DOI:
10.1016/j.bpj.2011.11.1529 - 发表时间:
2012-01-31 - 期刊:
- 影响因子:
- 作者:
Elizabeth Denning;Devarajan Thirumalai;Alexander D. MacKerell - 通讯作者:
Alexander D. MacKerell
Devarajan Thirumalai的其他文献
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{{ truncateString('Devarajan Thirumalai', 18)}}的其他基金
Physical Models for Cancer Cells with Links to Alterations in Genome Organization
与基因组组织改变相关的癌细胞物理模型
- 批准号:
2310639 - 财政年份:2023
- 资助金额:
$ 123.97万 - 项目类别:
Continuing Grant
Topics in Protein and RNA Folding and Dynamics
蛋白质和 RNA 折叠和动力学主题
- 批准号:
2320256 - 财政年份:2023
- 资助金额:
$ 123.97万 - 项目类别:
Standard Grant
Physical Models for Cancer Progression
癌症进展的物理模型
- 批准号:
1708128 - 财政年份:2017
- 资助金额:
$ 123.97万 - 项目类别:
Continuing Grant
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 - 财政年份:2016
- 资助金额:
$ 123.97万 - 项目类别:
Continuing Grant
INSPIRE: Minimal adaptive and replicating cell
INSPIRE:最小适应性和复制细胞
- 批准号:
1632756 - 财政年份:2016
- 资助金额:
$ 123.97万 - 项目类别:
Standard Grant
INSPIRE: Minimal adaptive and replicating cell
INSPIRE:最小适应性和复制细胞
- 批准号:
1523098 - 财政年份:2015
- 资助金额:
$ 123.97万 - 项目类别:
Standard Grant
Topics in protein and RNA folding and dynamics
蛋白质和 RNA 折叠和动力学主题
- 批准号:
1361946 - 财政年份:2014
- 资助金额:
$ 123.97万 - 项目类别:
Continuing Grant
Workshop: International Meeting on Protein Folding and Dynamics; to be held October 15-17, 2012 in Bangalore, India
研讨会:蛋白质折叠和动力学国际会议;
- 批准号:
1241302 - 财政年份:2012
- 资助金额:
$ 123.97万 - 项目类别:
Standard Grant
GRC: Protein Folding and Dynamics in Ventura, CA January 7-8, 2012
GRC:蛋白质折叠和动力学,加利福尼亚州文图拉,2012 年 1 月 7-8 日
- 批准号:
1157471 - 财政年份:2012
- 资助金额:
$ 123.97万 - 项目类别:
Standard Grant
Creation of POLS-SAVI Node at the University of Maryland
在马里兰大学创建 POLS-SAVI 节点
- 批准号:
1206005 - 财政年份:2012
- 资助金额:
$ 123.97万 - 项目类别:
Continuing Grant
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