COMPUTATIONAL ANALYSIS OF PROTEIN COMPLEX BINDING

蛋白质复合物结合的计算分析

• 批准号: 8171877
• 负责人: Lydia E. Kavraki
• 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/8171877
• 关键词: Algorithms; Amber; Binding; Binding Proteins; Code; Complement; Complement 3d; Complex; Computer Analysis; Computer Retrieval of Information on Scientific Projects Database; Computer software; Equilibrium; Fibrinogen; Free Energy; Funding; Grant; Human; Institution; Reaction; Research; Research Personnel; Resources; Source; Staging; Techniques; Thermodynamics; United States National Institutes of Health; Work; inhibitor/antagonist; molecular dynamics; mutant; protein complex; protein structure

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 work we will use non-linear dimensionality reduction techniques, in particular the Scalable Isomap (SciMap) approach, and molecular dynamics (MD) simulations on multiple protein structures to efficiently characterize the free energy landscape and the thermodynamics of the complexes formed by the Human Complement Component C3d and its inhibitor, the S. Auerus extra-cellular fibrinogen binding protein (Efb-C) and its mutants, R131A and N138A. The continuation of computational effort, initiated by the current DAC allocation, will consist of two main stages: 1. Enrichment of the conformational space spanned by the equilibrium ensemble by performing parallel MD simulations employing the AMBER software. 2. Characterization of the low energy landscapes of the obtained complexes by describing them by means of a small number of collective reaction coordinates via a non-linear parallel dimensionality reduction algorithm implemented through the SciMap code developed by our research group. As a result of this work we expect to obtain a detailed description of the low energy landscapes of the above mentioned bound complexes.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 在这项工作中，我们将使用非线性降维技术，特别是可扩展 Isomap (SciMap) 方法和对多种蛋白质结构的分子动力学 (MD) 模拟，以有效地表征由人类补体成分 C3d 及其抑制剂、S. Auerus 细胞外纤维蛋白原结合蛋白 (Efb-C) 及其形成的复合物的自由能景观和热力学特征。 突变体，R131A 和 N138A。由当前 DAC 分配启动的计算工作的延续将包括两个主要阶段： 1. 通过使用 AMBER 软件执行并行 MD 模拟来丰富平衡系综所跨越的构象空间。 2. 通过我们研究组开发的 SciMap 代码实现的非线性并行降维算法，通过少量集体反应坐标来描述所获得的配合物的低能景观，从而表征它们。作为这项工作的结果，我们期望获得上述结合配合物的低能量景观的详细描述。