The I-TASSER Suite: protein structure and function prediction

作者：Jianyi Yang, Renxiang Yan, Ambrish Roy, Dong Xu, Jonathan Poisson, Yang Zhang · 发表于：Nature Methods · 年份：2014 · DOI：10.1038/nmeth.3213 · 被引用次数：5333 · 研究领域：Medicine、Biology

The lowest free-energy conformations are identified by structure clustering. A second round of assembly simulation is conducted, starting from the centroid models, to remove steric clashes and refine global topology. Final atomic structure models are constructed from the low-energy conformations by a two-step atomic-level energy minimization approach. The correctness of the global model is assessed by the confidence score, which is based on the significance of threading alignments and the density of structure clustering; the residue-level local quality of the structural models and B factor of the target protein are evaluated by a newly developed method, ResQ, built on the variation of modeling simulations and the uncertainty of homologous alignments through support vector regression training. For function annotation, the structure models with the highest confidence scores are matched against the BioLiP5 database of ligand-protein interactions to detect homologous function templates. Functional insights on ligand-binding site (LBS), Enzyme Commission (EC) and Gene Ontology (GO) are deduced from the functional templates. We developed three complementary algorithms (COFACTOR, TM-SITE and S-SITE) to enhance function inferences, the consensus of which is derived by COACH4 using support vector machines. Detailed instructions for installation, implementation and result interpretation of the Suite can be found in the Supplementary Methods and Supplementary Tables 1 and 2. The I-TASSE...