Membrane Protein Structural Dynamics Consortium

膜蛋白结构动力学联盟

基本信息

批准号：
9149295
负责人：
Eduardo A Perozo
金额：
$ 287.75万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-08-10 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9149295
关键词：
Address Area Behavior Biological Biological Process Cell physiology Cells Communities Complex Computational Technique Computer Analysis Computing Methodologies Country Crystallization Data Equilibrium Goals Health Incubators Institution Internet Kinetics Knowledge Language Maps Measurement Measures Membrane Proteins Methods Molecular Conformation Molecular Machines Motion Movement Outcome Pathology Pathway interactions Phase Pilot Projects Positioning Attribute Protein Dynamics Proteins Research Research Infrastructure Research Personnel Resolution Role Shapes Side Signal Transduction Signaling Molecule Structure System Techniques Technology Time Vertebral column Work base biological systems biophysical model conformational conversion design innovation method development molecular dynamics movie multidisciplinary nanomachine nanoscale novel protein function protein structure scaffold single molecule technology development tool

项目摘要

DESCRIPTION (provided by applicant): To understand membrane proteins, one must ultimately be able to visualize how these complex nanoscale "molecular machines" move and change their shape atom-by-atom as a function of time while they perform their function. Grounded on the understanding that membrane proteins are dynamic entities that evolved to execute complex sets of movements to perform their functions, what is critically needed is a "conceptual movie" that captures the essential structural rearrangements underlying function. In spite of recent progress, any particular approach, albeit experimental or computational, is too limited to provide complete information about the transient features associated with such conformational transitions. To make a significant leap forward, the quantitative study of membrane protein dynamics requires a synergistic and multi-disciplinary effort. The main task of this 10-year Consortium is to quantitatively address these issues and provide a basic set of mechanistic principles that relate membrane protein structural dynamics to their function based on a set of membrane protein "archetypes". In this proposal, we highlight our recent advances in membrane protein crystallization, spectroscopic, biophysical and modeling techniques. Through highly collaborative partnerships that balance technology incubators (the scientific Cores) with specific projects (Bridging and Pilot projects) we have reached a level of applicability to complex systems unimaginable just a decade ago. However, dynamic information must be quantitatively determined to understand function and this requires the application of both known strategies and methods development. Our proposition remains that a tight integration between structural methods, spectroscopic techniques, functional analyses and computational approaches, is required to provide a deep understanding of these nano-machines and their biological roles. In its Phase II, we find ourselves in an excellent position to expand the number of systems under study, their overall complexity and incorporate new experimental and computational techniques. Accordingly, the MPSDC will continue to be organized around multidisciplinary project teams studying major mechanistic questions associated with membrane protein function in nine archetype systems, spanning a multiplicity of energy transduction mechanisms. Furthermore, the research infrastructure in place for phase II will extend the capacity of the Consortium to make further transforming contributions that should define the fundamental principles governing membrane protein function into the next decade

描述（由申请人提供）：为了理解膜蛋白，人们最终必须能够想象这些复杂的纳米级“分子机器”在执行其功能时如何随着时间的推移逐个原子地移动和改变它们的形状。了解膜蛋白是动态实体，进化为执行复杂的运动来执行其功能，迫切需要的是捕捉基本功能的基本结构重排的“概念电影”，尽管最近取得了进展，但任何特定的方法，然而实验或计算的能力太有限，无法提供与此类构象转变相关的瞬时特征的完整信息。为了取得重大飞跃，膜蛋白动力学的定量研究需要协同和多学科的努力。年联盟的目标是明确解决这些问题，并提供一套基本的机制原理，基于定量的一组膜蛋白“原型”将膜蛋白结构动力学与其功能联系起来。在这项提案中，我们重点介绍了我们在膜蛋白方面的最新进展。结晶 ,通过高度协作的伙伴关系，平衡技术孵化器（科学核心）与特定项目（桥接和试点项目），我们已经达到了对复杂的适用性水平。然而，必须定量确定动态信息才能理解功能，这需要应用已知的策略和方法开发，我们的主张仍然是结构方法、光谱技术、功能分析和计算方法之间的紧密结合。，需要深入了解这些纳米机器及其生物学作用。在第二阶段，我们发现自己处于有利地位，可以扩大正在研究的系统的数量、其整体复杂性并结合新的实验和计算技术。因此，MPSDC 将继续将围绕多学科项目团队组织起来，研究与九个原型系统中膜蛋白功能相关的主要机制问题，涵盖多种能量转导机制。此外，第二阶段的研究基础设施将扩展该联盟的能力，以进行进一步的转型应该定义未来十年控制膜蛋白功能的基本原则的贡献