MOLECULAR DYNAMIC SIMULATION OF THE INTERACTION OF THE ADAPTER WITH THE GENETIC

适配器与遗传相互作用的分子动力学模拟

• 批准号: 8171767
• 负责人: MARIA G KURNIKOVA
• 金额: $ 0.11万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171767
• 关键词: Algorithms; Award; Cereals; Characteristics; Computer Retrieval of Information on Scientific Projects Database; Development; Free Energy; Funding; Genetic; Glutamate Receptor; Grant; Institution; Investigation; Ion Channel; Ligands; Methodology; Modeling; Molecular; Pharmacy Schools; Potassium Channel; Proteins; Reaction; Request for Applications; Research; Research Personnel; Research Project Grants; Resources; Source; System; Testing; United States National Institutes of Health; Universities; Work; design; flexibility; globular protein; meetings; molecular dynamics; protein structure; receptor; simulation

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The research described in this proposal is continuation of projects previously supported by the NSF PACI grant #MCB040046 titled Molecular Simulations of the Ion Channel and Receptor proteins. In this application we request support for the second year of this multi-year award (04.01.2008-03.30.2010) and additional resources that are required due to expansion of our research projects. We are proposing to extend our studies to include additional systems and to test hypotheses which were formulated during our work in the previous period of funding. The majority of work included in this application is supported by current NIH R01 grant to PI, as well as a new funding to PI as a subcontract of an NIH R01 to Dr. P. Friedman of School of Pharmacy of the University of Pittsburgh. In this project we propose to hierarchically combine atomistic and coarse-grained geometric simulations of proteins to develop an efficient and practical algorithm to calculate potentials of mean force (PMF) along reaction coordinates connecting two known states. In order to design and test proposed methodological development we need to perform extensive MD simulations of protein systems of various sizes. The set of studies described in the following sections is designed such that it allows us to meet both our objectives: the study of ion channels and receptors, and methodology development for better understanding of protein flexibility and more accurate free energy calculations. We will continue to use our MD/FIRST methodology (Mamonova et al. Phys. Biol. 2005) to identify rigid and flexible regions in proteins and to correlate flexibility of protein structures with their functional characteristics. As a part of the original project investigation of the protein flexibility is continued using small globular proteins as test examples. We extend our studies to model ligand-protein interactions of the PDZ domains of NHERF1 protein, as well as free energy controlling pore closure in Glutamate Receptors and Potassium channels as an extension of our prior studies.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 本提案中描述的研究是先前由NSF PACI赠款#MCB040046支持的题为离子通道和受体蛋白质的分子模拟的项目的继续。在这份申请中，我们请求为这项多年奖励的第二年(2008年4月1日-2010年3月30日)提供支持，以及由于我们研究项目的扩大而需要的额外资源。我们提议将我们的研究扩大到包括更多的系统，并检验我们在上一次供资期间的工作中提出的假设。这项申请中包括的大部分工作都得到了目前NIH R01对PI的资助，以及作为匹兹堡大学药学院P.Friedman博士的NIH R01分包合同对PI的新资助。在这个项目中，我们建议将原子化和粗粒度的蛋白质几何模拟层次化地结合起来，以开发一种高效而实用的算法来计算连接两个已知状态的反应坐标上的平均力势(PMF)。为了设计和测试所提出的方法学发展，我们需要对不同大小的蛋白质系统进行广泛的MD模拟。以下部分描述的一系列研究的设计使我们能够满足我们的两个目标：离子通道和受体的研究，以及更好地了解蛋白质灵活性和更准确的自由能计算的方法开发。我们将继续使用我们的MD/First方法(Mamonova等人)。太棒了。比奥尔。2005)确定蛋白质中的刚性和柔性区域，并将蛋白质结构的灵活性与其功能特征联系起来。作为最初项目的一部分，继续使用小球状蛋白质作为测试样本来研究蛋白质的灵活性。我们将我们的研究扩展到NHERF1蛋白PDZ结构域的配体-蛋白质相互作用模型，以及控制谷氨酸受体和钾通道孔洞关闭的自由能，作为我们先前研究的扩展。