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 深入了解膜蛋白功能，将结构与 计算建模核心 D4（简称 CMC）是一个核心统一组件。 MPSDC 的组成部分，充当将实验数据组装成连贯的物理图片的“粘合剂”。 CMC 的目标是提供智力资源来开发、验证和应用新颖的技术 支持并与具体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集成和传播 MPSDC 和整个科学界的重点是计算。 通过启用有效和定量的方法可以增强和加深机械洞察力 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建模 分辨率计算框架来利用可以从不同的信息中获取的信息 一系列补充实验技术来发现和/或完善结构模型 膜蛋白可访问的不同功能形式/状态； 膜蛋白的表示（目标 2），我们将扩大开放获取网络的范围- 基于工具来进行最先进的计算并建立标准化的计算 实现膜蛋白最真实、最准确的物理表征的实验方案 系统；以及我们推进的构象转变途径和功能运动（目标 2） 用于确定大膜构象转变途径的模拟工具 蛋白质，并提供设计实验以通过计算测试和验证这些实验的方法 途径。