Membrane Protein Structural Dynamics Consortium

描述（由申请人提供）：膜蛋白在控制物质和信息进出细胞、确定能量的流动和使用以及触发许多信号传导途径的启动方面发挥重要作用。为了实现这些功能，构象和相互作用动力学对它们的功能行为产生了主导影响，因为结构和动力学之间的相互作用最终决定了它们的功能。膜蛋白结构动力学联盟（MPSDC）是一个高度互动，紧密集成和多学科的努力，专注于阐明各种膜蛋白的结构，动力学和功能之间的关系。 MMPSD将围绕由来自五个不同国家的14个机构的调查人员组成的多学科项目小组进行组织。这些团队将研究与膜蛋白功能相关的主要机制问题，因为它涉及两个主要领域：信号传导中的能量转导（离子通道和受体）和能量相互转换（转运蛋白和泵）。最终，我们的目标是通过解剖和分析这些功能的分子和动力学基础，在前所未有的定量水平上，以及利用这些信息将改变的和新的活动工程化到膜蛋白框架中，以合理地进化新的功能，来解码管理蛋白质运动及其相关波动动力学的一般机械原理。为了实现其目标，MPSDC将并行开发一套工具、概念和试剂，以：1）应用最先进的光谱方法（磁共振、荧光、2D-IR）跟踪确定结构的构象变化和动力学; 2）将动力学测量与高分辨率系综和单分子功能测量相关联; 3）设计并实现了新的计算方法，将静态和动态数据与函数联系起来。六个核心设施将以高度互动的方式与各个项目相互连接。这些核心将作为“创新孵化器”和研究支持中心，在以下关键领域提供服务和专业知识：膜蛋白表达，建立探针和去污剂的化学合成能力，生成多种结合剂和其他结晶伴侣等靶向结合剂，开发通用计算工具来解释和整合丰富的实验数据新的、高度特异性的合成毒素的产生，以及通过使用宏基因组学工具不断发现新的靶点。

DESCRIPTION (provided by applicant): Membrane proteins play an essential role in controlling the movement of material and information in and out of the cell, in determining the flow and use of energy, as well as in triggering the initiation of numerous signaling pathways. To fulfill these roles, conformational and interaction dynamics exert a dominant influence on their functional behavior, for it is the interplay between structure and dynamics what ultimately defines their function. The Membrane Protein Structural Dynamics Consortium (MPSDC) is proposed as a highly interactive, tightly integrated and multidisciplinary effort focused on elucidating the relationship between structure, dynamics and function in a variety of membrane proteins. The MMPSD will be organized around multidisciplinary project teams formed by investigators from 14 institutions in five different countries. These teams will study major mechanistic questions associated with membrane protein function as it relates to two major areas: energy transduction in signaling (ion channels and receptors) and energy inter-conversion (transporters and pumps). Ultimately, our goal is to decode the general mechanistic principles that govern protein movement and its associated fluctuation dynamics by dissecting and analyzing the molecular and dynamical bases of these functions at an unprecedented and quantitative level, as well as exploiting this information to engineer altered and novel activities into membrane protein frameworks to rationally evolve new functions. To accomplish its goals, the MPSDC will develop in parallel a set of tools, concepts and reagents to: 1) Apply state of the art spectroscopic methods (Magnetic Resonance, Fluorescence, 2D-IR) to follow conformational changes and dynamics of the determined structures; 2) Correlate dynamic measurements with high-resolution ensemble and single molecule functional measurements; and 3) Design and implement novel computational approaches to link static and dynamic data with function. Six core facilities will feed and interconnect with the individual projects in a highly interactive way. The cores will act as both, "innovation incubators" and research support centers by providing service and expertise In these critical areas: Membrane protein expression, the establishment of chemical synthesis capabilities for probes and detergents, the generation of a variety of binders and other crystallization chaperones and other target binders, the development of common computational tools to interpret and integrate the wealth of experimental data, the generation of novel, highly specific synthetic toxins and the continuous discovery of novel targets through the use of metagenomics tools.