STUDY OF PROTEIN DYNAMICS UNDER HIGH HYDROSTATIC PRESSURE

高静水压下蛋白质动力学的研究

• 批准号: 8364112
• 负责人: PETER P BORBAT
• 金额: $ 0.37万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8364112
• 关键词: Collaborations; Development; Frequencies; Funding; Grant; Hydrostatic Pressure; Laboratories; Methods; Myoglobin; National Center for Research Resources; Physiologic pulse; Principal Investigator; Protein Dynamics; Proteins; Research; Research Infrastructure; Resources; Source; Spin Labels; Technology; Time; United States National Institutes of Health; conformer; cost; interest; molecular dynamics; pressure; protein folding; tool

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. ACERT has a long-standing collaboration with Wayne Hubbell, fueled by common interests in the study of molecular dynamics including protein dynamics. It has been shown recently by Wayne Hubbell that application of high hydrostatic pressure of up to 2 kbar populates higher energy conformers, and thereby enables one to detect dynamic exchange between the ground state and excited state, which is strongly believed to be functional. Hubbell has shown that these states can be probed by CW ESR and pulse saturation ESR. Since these states can undergo exchange on a microsecond time-scale, it would be logical to apply 2D ELDOR to study protein dynamics and conformational exchange in proteins under high pressure. This presents a great opportunity for 2D ELDOR to realize its potential in studying molecular dynamics. We will conduct the study initially on two spin-labeled proteins: Myoglobin and IFABP, which Hubbell's laboratory has already produced. It should be noted that the development of a 2D ELDOR high pressure method has broader implications, for example, by providing more tools to study by 2D-ELDOR protein folding, both in the steady state with or without denaturant and kinetically after a pressure jump. Furthermore, 2D-ELDOR at high pressure can be conducted at ACERT in a multi-frequency context, which would help to determine dynamic variables with greater confidence

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 Acert与韦恩·哈伯尔（Wayne Hubbell）进行了长期的合作，这是在包括蛋白质动力学在内的分子动力学研究中的共同利益。最近，韦恩·哈伯尔（Wayne Hubbell）显示了高达2 kbar的高静水压力的应用可填充更高的能量构象异构体，从而使一个人能够检测基态和激发态之间的动态交换，这被认为是功能性的。 Hubbell表明，可以通过CW ESR和脉冲饱和ESR探测这些状态。 由于这些状态可以在微秒的时间尺度上进行交换，因此在高压下使用2D ELDOR研究蛋白质动力学和构象交换是合乎逻辑的。 这为2D Eldor提供了一个很好的机会，可以实现其研究分子动力学的潜力。我们最初将对两种自旋标记蛋白进行研究：肌红蛋白和IFABP，Hubbell的实验室已经生产了。应当指出的是，2D Eldor高压法的发展具有更广泛的含义，例如，通过提供更多的工具来通过2D-Eldor蛋白折叠进行研究，无论是在压力跳增之后带有或没有变性的稳定状态。此外，可以在多频率的情况下在ACERT上进行高压下的2D-Eldor，这将有助于以更大的置信度确定动态变量