Computational Modeling Core

膜蛋白质结构动力学联合会(MPSDC)内的所有努力都旨在 对膜蛋白功能有深入的机制理解，将结构与 动力学。计算建模核心D4，称为CMC，是一个中央统一组件 作为粘合剂，将实验数据组合成一幅连贯的物理图像。 CMC的目标是提供智力资源来开发、验证和应用 方法和技术，支持和结合 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 通过实现有效和量化来增强和深化机械性洞察力的方法 与实验数据进行了比较。中央军委的研究计划围绕三个方面组织。 具体目标：多分辨率结构建模(Aim 1)，在此我们开发了一个集成的多分辨率结构建模 解决方案计算框架，以利用可以从不同的 一系列补充实验技术，用于发现和/或改进结构模型 膜蛋白可获得的不同功能形式/状态；力场和物理 膜蛋白的表达(目标2)，我们将扩大开放获取网络的范围- 基于工具执行最先进的计算并建立标准化计算 实现膜蛋白最真实和最准确的物理表示的协议 系统；以及构象转换路径和功能运动(目标2) 确定大分子膜构象转变途径的模拟工具 蛋白质，并提供设计实验的手段来测试和验证这些计算 小路。

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.