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。 在这项工作中，我们将使用非线性降低降低技术，尤其是可伸缩的ISOMAP（SCIMAP）方法，以及对多种蛋白质结构上的分子动力学（MD）模拟，以有效地表征自由能景观和由人类补体C3D和IT抑制剂构成的型号和型号的构造形成的络合物的热力学，并表征其抑制剂。突变体，R131A和N138A。当前DAC分配发起的计算工作的延续将由两个主要阶段组成：1。通过使用Amber软件进行平行的MD模拟，通过平衡集合跨越了构象空间。 2。通过少数集体反应坐标通过我们的研究小组开发的SCIMAP代码实现的非线性平行尺寸降低算法来描述所获得的复合物的低能景观。由于这项工作，我们希望获得上述结合复合物的低能景观的详细描述。