CAPTURING LARGE-SCALE STRUCTURAL TRANSITIONS IN MEMBRANE TRANSPORTERS AT ATOMIC

捕获原子膜转运蛋白的大规模结构转变

• 批准号: 8364328
• 负责人: Emad Tajkhorshid
• 金额: $ 0.11万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8364328
• 关键词: Automobile Driving; Binding; Biomedical Research; Cells; Coupling; Event; Funding; Grant; High Performance Computing; Life; Membrane Transport Proteins; Molecular Machines; National Center for Research Resources; Nature; Principal Investigator; Proteins; Research; Research Infrastructure; Resources; Source; Time; United States National Institutes of Health; cost; simulation

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We request allocation on Anton for extended MD simulations that will investigate several membrane transporters representing major energy-coupling mechanisms of transport in living cells. The proposed studies will characterize the nature and magnitude of protein conformational changes induced by binding/unbinding of the substrate and the driving energy-coupling events on a microsecond time scale, and reveal structurally unknown states of the transporters. The results will bring an unprecedented time scale to the dynamical description of these slow molecular machines for the first time, and given the experimental inaccessibility of such information, will revolutionize our mechanistic view of their function.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的首席研究员可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 我们请求在 Anton 上进行扩展 MD 模拟的分配，该模拟将研究代表活细胞中运输的主要能量耦合机制的几种膜转运蛋白。拟议的研究将表征底物结合/解结合引起的蛋白质构象变化的性质和程度以及微秒时间尺度上的驱动能量耦合事件，并揭示转运蛋白的结构未知状态。 研究结果将首次为这些慢分子机器的动态描述带来前所未有的时间尺度，并且考虑到此类信息在实验上无法获得，将彻底改变我们对其功能的机械观点。