STRUCTURAL AND THERMODYNAMICAL PROPERTIES OF COMPLEXES FORMED BY THE HUMAN COMP

人类复合物形成的结构和热力学性质

• 批准号: 7956267
• 负责人: Lydia E. Kavraki
• 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/7956267
• 关键词: Algorithms; Amber; Amino Acids; Binding; Binding Proteins; Biomedical Research; Complement; Complement 3d; Complex; Computer Retrieval of Information on Scientific Projects Database; Equilibrium; Fibrinogen; Free Energy; Funding; Generations; Grant; High Performance Computing; Housing; Human; Institution; Modeling; Molecular Conformation; Nature; Production; Property; Research; Research Personnel; Resources; Running; Sampling; Source; Spottings; Staging; Staphylococcus aureus; Structure; System; Techniques; United States National Institutes of Health; Work; extracellular; molecular dynamics; mutant; protein complex

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. In this initial study we aim to estimate the structural and thermodynamical binding properties of the complex formed by the Human Complement component C3D and the inhibitory domain of S. aureus extracellular fibrinogen-binding protein (Efb-C), and two of its mutants. The complex contains 362 amino acids. Our work will proceed in two main stages: 1. Sampling of the conformational space of the bound complex by generating an ensemble of low-energy conformations using an in-house developed loop modeling algorithm and by subsequently minimizing the generated conformations using the standard Amber 9 package. While the loop generation stage is embarrassingly parallel in nature the minimization technique involves significant amount of message passing due to the systems' large size (approximately 6000 atoms for the complexed protein with all-atom representation). 2. Estimating equilibrium properties of selected sampled conformations obtained in the previous stage. The estimated properties include binding free energy and specific interaction energy for the wildtype complex and its mutants. This will be done using Molecular Dynamics simulations on selected resulting structures through the Amber 9 package and will rely on the utilization of the Amber's massively parallel capabilities. The Teragrid start-up allocation will allow us to: a. Perform the efficiency studies and identify the number of processors which will provide a "sweet spot" for the Amber production runs. b. Find the optimal submit strategy for the loop generation stage runs. c. Perform first production runs and generate publishable results.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 在这项最初的研究中，我们旨在估计由人补体成分C3D和金黄色葡萄球菌外细胞纤维蛋白原结合蛋白（EFB-C）及其两个突变体形成的复合物的结构和热力学结合特性。该络合物含有362个氨基酸。我们的工作将在两个主要阶段进行：1。通过使用内部开发的环路建模算法产生低能量构象的合奏，并随后使用标准Amber 9软件包来最大程度地减少生成的构型，从而对结合复合物的构象空间进行采样。尽管循环生成阶段本质上是令人尴尬的平行，但最小化技术涉及由于系统的大尺寸而引起的大量消息传递（大约6000个具有全原子代表的复合蛋白的原子）。 2。估计上一阶段获得的选定采样构象的平衡特性。估计的特性包括野生型复合物及其突变体的结合自由能和特定相互作用能。这将使用分子动力学模拟通过Amber 9软件包对所选的结构进行，并依赖于琥珀大量平行功能的利用。 TeraGRID启动分配将使我们能够：进行效率研究并确定将为琥珀生产提供“最佳位置”的处理器数量。 b。找到循环生成阶段运行的最佳提交策略。 c。执行首次生产运行并生成可发布的结果。