DYNAMICS AND RIGIDITY/FLEXIBILITY OF THERMOPHILIC AND MESOPHILIC PROTEINS

嗜热和嗜温蛋白质的动力学和刚性/柔性

• 批准号: 7956304
• 负责人: MARIA G KURNIKOVA
• 金额: $ 0.08万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7956304
• 关键词: Biomedical Research; Computer Retrieval of Information on Scientific Projects Database; Funding; Genets; Goals; Grant; Graph; High Performance Computing; Homologous Protein; Hydrogen Bonding; Institution; Methods; Molecular Models; Muscle Rigidity; Physics; Property; Proteins; Research; Research Personnel; Resources; Sodium Chloride; Solutions; Source; Structure; Triad Acrylic Resin; United States National Institutes of Health; alpha helix; arginylglutamate; base; flexibility; lysylglutamic acid; molecular dynamics; molecular modeling; protein structure; theories

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 goals of this project is to systematically investigate how rigidity/flexibility varies among homologous structural domains of thermophilic and mesophilic proteins, to understand whether the rigidity/flexibility of thermophilic and mesophilic proteins correlate with their stability, and whether both properties are controlled by the same structural determinants. The method used in this study is a hierarchical physics based molecular modeling approach termed MD/FIRST (Mamonova, Phys. Biol. 2005), which combines the molecular dynamics (MD) simulations of a native structure protein in solution with a rigid cluster decomposition method FIRST based on the graph theory (Jacobs, Proteins: Struct., Funct., Genet. 2001). Using this approach we found that there are two groups of proteins. First one is characterized the salt bridge or ionic network. This network includes salt bridge triads Agr-Glu_Lys, Arg-Glu-Arg or salt bridges (like Arg-Glu) connected with hydrogen bonds. This ionic network accumulates alpha helixes and rigidifies the structure. The second groups can be characterized by the single salt bridges and h-bonds or small ionic clusters. Such difference in the network of salt bridges results in different flexibility of homologous protein. MD/FIRST approach allows for characterizing structural features in atomic detail that determine the rigidity/flexibility of a protein structure.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 该项目的目标是系统地研究嗜热蛋白和嗜温蛋白的同源结构域之间的刚性/柔性如何变化，以了解嗜热蛋白和嗜温蛋白的刚性/柔性是否与其稳定性相关，以及这两种性质是否由相同的结构决定因素控制。本研究中使用的方法是基于分层物理学的分子建模方法，称为MD/FIRST（Mamonova，Phys.Biol.2005），其将溶液中天然结构蛋白质的分子动力学（MD）模拟与基于图论的刚性簇分解方法FIRST（Jacobs，Proteins：Struct.，功能，Genet. 2001年）。使用这种方法，我们发现有两组蛋白质。第一种是盐桥或离子网络。该网络包括与氢键连接的盐桥三联体Agr-Glu_Lys、Arg-Glu-Arg或盐桥（如Arg-Glu）。这种离子网络积累α螺旋并使结构刚性化。第二组的特征在于单盐桥和氢键或小离子簇。盐桥网络的这种差异导致同源蛋白质的不同柔性。MD/FIRST方法允许在原子细节中表征决定蛋白质结构的刚性/柔性的结构特征。