COMPUTATIONAL ANALYSIS OF PROTEIN COMPLEX BINDING

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在这项工作中，我们将使用非线性降维技术，特别是可伸缩的ISOMAP(SciMap)方法，和对多个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、金黄色葡萄球菌胞外纤维蛋白原结合蛋白(EFB-C)及其突变体R131A和N138A形成的复合体的自由能景观和热力学。当前DAC分配所启动的计算工作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跨越的构象空间。2.通过我们课题组开发的SciMap程序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络合物的低能景观。作为这项工作的结果，我们期望得到上述结合络合物的低能景观的详细描述。

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.