DEVELOPMENT AND APPLICATION OF A HIERARCHICAL PROTOCOL FOR AB INITIO PREDICTION

该子项目是利用资源的许多研究子项目之一 由NIH/NCRR资助的中心赠款提供。次级项目的主要支助 而子项目的主要调查员可能是由其他来源提供的， 包括其他NIH来源。 为子项目列出的总成本可能 表示子项目使用的中心基础设施的估计数量， NCRR赠款不直接向子项目或子项目工作人员提供资金。 目前计算生物学和生物信息学的研究主要集中在预测蛋白质的三维结构上。研究者们正试图通过不同的方法来开发仅基于氨基酸序列的蛋白质结构预测方法。然而，仅仅三维结构不足以理解许多涉及蛋白质的生物过程。在这项建议中提出的研究是基于我们的基于物理学的粗粒度力场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，而且还使用有关其折叠机制和热力学稳定性的信息。我们期望这样的参数化和广泛的构象空间搜索使用分子动力学，使我们能够同时预测两个蛋白质的性质：结构和热力学稳定性的天然状态和折叠途径（S），导致从未折叠到折叠状态。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Most of current research in computational biology an bioinformatics is focused on predicting the three-dimensional structure of proteins. Using different approaches, researches are trying to develop methodology for predicting proteins structure based only on amino acid sequence. However, three-dimensional structure alone is not sufficient to understand many biological processes which involve proteins. Research presented in this proposal is based on parameterization of our physics-based coarse-grained force-filed 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 parameterization and extensive conformational space search using molecular dynamics 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.