Computational Modeling Core

计算建模核心

• 批准号: 9351544
• 负责人: BENOIT ROUX
• 金额: $ 46.82万
• 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: 2010-08-10 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9351544
• 关键词: Address; Biological Process; Communities; Complex; Computer Simulation; Computing Methodologies; Data; Deer; Development; Disease; Ensure; Environment; Equilibrium; Fluorescence Resonance Energy Transfer; Glues; Goals; Harvest; Information Theory; Internet; Investigation; Knowledge; Ligand Binding; Link; Lipids; Membrane Proteins; Metals; Methodology; Methods; Modeling; Molecular Conformation; Molecular Machines; Molecular Probes; Motion; Motivation; Movement; Mutation; Online Systems; Pathway interactions; Periodicity; Pharmacologic Substance; Plant Roots; Protocols documentation; Research; Resolution; Resources; Roentgen Rays; Role; Sampling; Shapes; Standardization; Structural Models; Structural Protein; Structure; System; Techniques; Technology; Testing; Visit; advanced simulation; base; computer framework; computerized tools; conformational conversion; crosslink; design; experimental study; insight; luminescence resonance energy transfer; molecular scale; mutant; novel; programs; protein function; protonation; response; simulation; tool; web-based tool

All efforts within the Membrane Protein Structural Dynamics Consortium (MPSDC) are aimed at gaining a deep mechanistic understanding of membrane protein function, linking structure to dynamics. The Computational Modeling Core D4, referred to as CMC, is a central unifying component of the MPSDC, serving as the “glue” to assemble experimental data into a coherent physical picture. The goals of the CMC are to provide an intellectual resource to develop, validate and apply novel methods and technologies that support and integrate with the specific experimental studies in the MPSDC, as well as to facilitate the integration and dissemination of these computational methods within the MPSDC and the scientific community at large. Emphasis is placed on computational approaches that can enhance and deepen mechanistic insight by enabling valid and quantitative comparisons with experimental data. The research plan of the CMC is organized around three Specific Aims: Multi-Resolution Structural Modeling (Aim 1), where we develop an integrated multi- resolution computational framework to leverage the information that can be harvested from a diverse range of complementary experimental techniques to discover and/or to refine structural models of the different functional forms/states accessible to membrane proteins; Force Fields and Physical Representation of Membrane Proteins (Aim 2), where we will broaden the scope of open-access web- based tools to carry out state-of-the-art computations and establish standardized computational protocols to achieve the most realistic and accurate physical representation of membrane protein systems; and Conformational Transition Pathways and Functional Motions (Aim 2) where we advance the simulation tools for the determination of conformational transition pathways in large membrane proteins, and provide means to design experiments to test and validate those computational pathways.

膜蛋白结构动力学联盟（MPSDC）的所有努力都旨在 获得膜蛋白功能的深入机械理解，将结构与 动力学计算建模核心D4（简称CMC）是一个中心统一组件 作为“粘合剂”，将实验数据组装成一幅连贯的物理图像。 CMC的目标是提供一个智力资源，以开发，验证和应用新的 方法和技术，支持和整合的具体实验研究， MPSDC，以及促进这些计算方法的整合和传播 在MPSDC和整个科学界。重点放在计算 方法，可以增强和深化机制的洞察力，使有效的和定量的 与实验数据的比较。CMC的研究计划围绕三个方面进行组织 具体目标：多分辨率结构建模（目标1），我们开发了一个集成的多分辨率结构模型。 分辨率计算框架，以利用可以从各种 一系列互补的实验技术，以发现和/或完善的结构模型， 膜蛋白可进入的不同功能形式/状态;力场和物理 膜蛋白的表示（目标2），我们将扩大开放获取网络的范围， 的工具来进行最先进的计算，并建立标准化的计算 协议，以实现最真实和准确的物理表示膜蛋白 系统;和构象转换途径和功能运动（目标2），我们在其中推进 确定大分子膜构象转变途径的模拟工具 蛋白质，并提供手段来设计实验，以测试和验证这些计算 途径。