I-TASSER based atomic-level protein structure prediction

描述(申请人提供)：项目摘要：近年来的CASP实验在基于计算机的蛋白质三级结构预测方面取得了重大进展。最先进的算法，如Tasser，可以在不使用同源模板的情况下为2/3的单域蛋白质生成正确的折叠。大多数机型都是低成本的 分辨率的均方根(RMSD)为3-6埃，这可能是有用的蛋白质拓扑分析和一定程度的生物功能推断。然而，这样的模型并不适用于可靠的配体筛选。这项研究旨在为原子级高分辨率蛋白质结构建模开发新的方法。具体目标是：(1)开发用于原子级蛋白质结构建模的新算法--原子-Tasser；(2)开发用于低分辨率拓扑构建和高分辨率精化的两级复合势；(3)结构和序列相空间中的力场优化；(4)大规模基准原子-Tasser算法。总体而言，这些研究旨在扩大简化建模方法的有效性范围，并在三级结构预测的最新水平上提供显著改进。其目标是提高基于计算机的建模的准确性水平，特别是对于远距离/弱同源的蛋白质，以便它们能够真正用于 新药筛选和生化功能推断。

DESCRIPTION (provided by applicant): Project Summary: Recent years' CASP experiments have seen significant progress on computer-based protein tertiary structure prediction. The state-of-the-art algorithms, such as TASSER, can generate correct folds for 2/3 of single domain proteins without using homologous templates. Most of the models are of low resolution with a root mean square deviation (RMSD) 3-6 Angstroms, which may be useful for protein topology analysis and some level of biological function inference. However, such models are not suitable for reliable ligand screening. The proposed research seeks to develop new methodologies for the atomic-level high-resolution protein structure modeling. The specific aims are: (1) development of a new algorithm, atom-TASSER, for atomic-level protein structure modeling; (2) development of a two-level composite potential for both the low-resolution topology construction and the high-resolution refinement; (3) force field optimization in both structure and sequence phase spaces; (4) large-scale benchmarking of atom-TASSER algorithm. Overall, these studies are designed to extend the range of validity of the reduced modeling approaches, and provide significant improvements in the state-of-the-art of tertiary structure prediction. The goal is to push up the level of accuracy of computer-based modeling, especially for the distant/weakly homologous proteins, so that they can be of real use to new drug screening and biochemical functional inference.