MICRO-SECOND MOLECULAR DYNAMICS SIMULATION OF THE FOLDING PATHWAYS OF TETRATRIC

Tetratric折叠路径的微秒分子动力学模拟

• 批准号: 8364207
• 负责人: CAROL A PARISH
• 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/8364207
• 关键词: Behavior; Binding; Biomedical Research; Computer software; Data; Funding; Grant; High Performance Computing; Hour; Kinesin; Methods; Modeling; Motor; National Center for Research Resources; Pathway interactions; Physical condensation; Principal Investigator; Proteins; Research; Research Infrastructure; Resources; Solvents; Source; Structure; United States National Institutes of Health; base; cost; insight; mathematical model; molecular dynamics; protein folding; simulation; supercomputer; three dimensional structure

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 are requesting node hours on the Anton supercomputer in order to determine the tertiary structure of the tetratricopeptide repeat unit in the cargo binding domain of a kinesin motor protein. Preliminary data obtained using the Desmond molecular dynamics software with standard force fields and explicit solvent models suggests that this ~200 residue domain is a "fast-folder" and likely follows the nucleation-condensation folding mechanism. In addition to determining the 3D structure of an important and biologically functional domain, the ensemble of structures obtained from a multi-microsecond simulation will enable a fundamental analysis of the applicability of various protein folding models and provide structural insight into misfolded and semi-folded states that are not accessible to experimental methods. These results will also be utilized to exhaustively validate the suitability of lattice-based mathematical models for describing folding behavior of repeat proteins.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 我们在Anton超级计算机上请求节点小时数，以便确定运动蛋白马达蛋白的货物结合域中四肽重复单元的三级结构。利用Desmond分子动力学软件和标准力场和显式溶剂模型获得的初步数据表明，这个~200残基结构域是一个“快速文件夹”，可能遵循成核-凝聚折叠机制。除了确定一个重要的生物功能结构域的3D结构外，从多微秒模拟获得的结构集合将能够对各种蛋白质折叠模型的适用性进行基本分析，并提供对实验方法无法获得的错误折叠和半折叠状态的结构洞察。这些结果也将被用来详尽地验证基于晶格的数学模型对描述重复蛋白折叠行为的适用性。