Core D4: Computational Modeling

核心 D4：计算建模

• 批准号: 7922837
• 负责人: BENOIT ROUX
• 金额: $ 66.92万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7922837
• 关键词: Address; Arts; Biological Process; Chemicals; Communities; Complex; Computer Simulation; Computing Methodologies; Data; Databases; Development; Disease; Ensure; Fluorescence Resonance Energy Transfer; Goals; Grant; Harvest; Investigation; Knowledge; Link; Membrane Proteins; Metals; Methodology; Methods; Modeling; Molecular; Molecular Conformation; Molecular Machines; Motion; Movement; Mutation; Online Systems; Pathway interactions; Play; Process; Protocols documentation; Reaction; Research; Research Personnel; Resolution; Resources; Roentgen Rays; Role; Services; Shapes; Signal Transduction; Simulate; Structure; System; Technology; Testing; Validation; Visit; crosslink; design; interdisciplinary collaboration; luminescence resonance energy transfer; mutant; novel; programs; protein function; research study; simulation; tool; user-friendly

All the efforts within the Membrane Protein Structural Dynamics Consortium (MPSD) are aimed at gaining a deep mechanistic perspective on membrane protein function, linking structure to dynamics. Computation is expected to play a fundamental role in this process, as every Bridging Project (BP) comprises a computational component aiming to (1) analyze results, (2) help interpret structural and dynamical data, and (3) construct models/hypotheses to make predictions that will be tested experimentally in an iterative process that takes advantage of the wide range of interdisciplinary collaborations and resources enabled by this grant. For these reasons, the proposed Computational Modeling Core D4, referred to as CMC, is a central unifying component of the Consortium offering shared perspectives and correlated mechanistic interpretations among the BPs by virtue of ovedapping teams and common validated approaches. Membrane proteins can be considered to function as "molecular machines" that need to change shape and visit many conformational states to perform their function, mostly through complex allosteric mechanisms. To understand how membrane proteins perform such functions, and how this function is regulated and/or modified by disease (e.g., naturally occurring mutations), it is necessary to have detailed knowledge about all those conformational states as well as the reaction pathway connecting them. A profound mechanistic understanding of membrane proteins and their biological function will be recognized by one's ability to make quantitative and accurate predictions of structure, dynamics and function from computational models. Undeniably, sophisticated computations are already an integral part of biomolecular research on membrane proteins [1, 2]. Nonetheless, the collaborative research undertaken with the BPs in this Grant points out that current methodologies would significantly benefit from a more unified approach across multiple scales, and from a close integration of computational and experimental efforts. The computational approaches would also have a greater impact if they became more routinely accessible to all investigators (experimentalists and theoreticians alike). Clearty, additional advances and improvements are needed to address the challenging problems presented by membrane protein systems. A judicious long-term strategy about the role of computation in the investigation of biomolecular systems must ensure that efforts are invested to respond to both the need for dissemination and impact, and the continued development of novel methodologies. This view is incorporated in the overall goal of the CMC to provide and develop state-of-the-art methods and "tools" required for studying the mechanisms of function of complex membrane protein systems.

膜蛋白结构动力学联盟（MPSD）的所有努力都旨在获得膜蛋白功能的深层机制视角，将结构与动力学联系起来。计算预计将在这一过程中发挥基本作用，因为每个桥接项目（BP）都包含一个计算组件，旨在(1)分析结果，(2)帮助解释结构和动态数据，(3)构建模型/假设，以做出预测，这些预测将在利用该基金支持的广泛跨学科合作和资源的迭代过程中进行实验测试。