DEVELOPMENT AND APPLICATION OF A HIERARCHICAL PROTOCOL FOR AB INITIO PREDICTION

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。 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。研究人员正在尝试使用不同的方法开发仅基于氨基酸序列预测蛋白质结构的方法。然而，仅凭三维结构不足以理解涉及蛋白质的许多生化过程。该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，不仅使用有关蛋白质天然状态的三维结构的信息，还使用有关其折叠机制和热力学稳定性的信息。我们期望使用分子动力学的这种参数化和广泛的构象空间搜索将使我们能够同时预测两种蛋白质特性：天然状态的结构和热力学稳定性以及从展开状态到折叠状态的折叠途径。

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.