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.

膜蛋白结构动力联盟（MPSDC）中的所有努力均针对 获得对膜蛋白功能的深刻机械理解，将结构联系起来 动力学。计算建模核心D4（称为CMC）是中心统一组件 MPSDC的“胶水”，将实验数据组装成连贯的物理图片。 CMC的目标是提供一种智力资源来开发，验证和应用小说 支持并与特定实验研究相结合的方法和技术 MPSDC，以及促进这些计算方法的整合和传播 在MPSDC和整个科学界内。重点放在计算上 通过实现有效和定量的方法可以增强和加深机理见解的方法 与实验数据进行比较。 CMC的研究计划大约是三个 具体目的：多分辨率结构建模（AIM 1），在其中我们开发了一个综合的多个多分辨率建模 决议计算框架以利用潜水员可以收集的信息 发现和/或完善的完善实验技术范围 膜蛋白可访问的不同功能形式/状态；力场和身体 膜蛋白的表示（AIM 2），我们将扩大开放式网络的范围 基于进行最先进计算并建立标准化计算的工具 实现膜蛋白最现实，最准确的物理表示的协议 系统；以及构象过渡途径和功能运动（AIM 2）我们进步 用于确定大膜中构象过渡途径的仿真工具 蛋白质，并提供设计实验的方法来测试和验证这些计算 途径。