DEVELOPMENT AND APPLICATION OF A HIERARCHICAL PROTOCOL FOR AB INITIO PREDICTION

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。 目前计算生物学和生物信息学的大部分研究都集中在预测蛋白质的三维结构上。使用不同的方法，研究人员正试图开发仅基于氨基酸序列预测蛋白质结构的方法。然而，仅有三维结构并不足以理解许多涉及蛋白质的生化过程。本提案中提出的研究基于我们基于物理的粗粒度力场UNRES的参数化，不仅使用关于蛋白质天然状态的三维结构的信息，而且使用关于其折叠机制和热力学稳定性的信息。我们期望这种参数化和广泛的分子动力学构象空间搜索将使我们能够同时预测蛋白质的两个性质：天然状态的结构和热力学稳定性以及从未折叠到折叠状态的折叠路径(S)。

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. Most of current research in computational biology and bioinformatics is focused on predicting the three-dimensional structure of proteins. Using different approaches, researchers are trying to develope methodology for predicting protein structure based only on amino acid sequence. However, three-dimensional structure alone is not sufficient to understand many biochemical processes which involve proteins. Research presented in this proposal is based on parametrization of our physics-based coarse-grained force-field UNRES, using information not only about the three-dimensional structure of the native state of proteins but also about their folding mechanism and thermodynamic stability. We expect that such parametrization and extensive conformational space search using molecular dynamics will enable us to simultaneously predict two protein properties: structure and thermodynamic stability of the native state and folding pathway(s) which lead from the unfolded to the folded state.