title: Integration of QUARK and I-TASSER for Ab Initio Protein Structure Prediction in CASP11.
abstract: We tested two pipelines developed for template-free protein structure prediction in the CASP11 experiment. First, the QUARK pipeline constructs structure models by reassembling fragments of continuously distributed lengths excised from unrelated proteins. Five free-modeling (FM) targets have the model successfully constructed by QUARK with a TM-score above 0.4, including the first model of T0837-D1, which has a TM-score = 0.736 and RMSD = 2.9 Å to the native. Detailed analysis showed that the success is partly attributed to the high-resolution contact map prediction derived from fragment-based distance-profiles, which are mainly located between regular secondary structure elements and loops/turns and help guide the orientation of secondary structure assembly. In the Zhang-Server pipeline, weakly scoring threading templates are re-ordered by the structural similarity to the ab initio folding models, which are then reassembled by I-TASSER based structure assembly simulations; 60% more domains with length up to 204 residues, compared to the QUARK pipeline, were successfully modeled by the I-TASSER pipeline with a TM-score above 0.4. The robustness of the I-TASSER pipeline can stem from the composite fragment-assembly simulations that combine structures from both ab initio folding and threading template refinements. Despite the promising cases, challenges still exist in long-range beta-strand folding, domain parsing, and the uncertainty of secondary structure prediction; the latter of which was found to affect nearly all aspects of FM structure predictions, from fragment identification, target classification, structure assembly, to final model selection. Significant efforts are needed to solve these problems before real progress on FM could be made. Proteins 2016; 84(Suppl 1):76-86. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, 48109.|Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan, 48109.
authors.forename: Wenxuan
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, 48109.|Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan, 48109.
authors.forename: Jianyi
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, 48109.|Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan, 48109.
authors.forename: Baoji
authors.initials: B
authors.lastname: He
authors.affiliation: Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, 48109.|Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan, 48109.
authors.forename: Sara Elizabeth
authors.initials: SE
authors.lastname: Walker
authors.affiliation: Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, 48109.|Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan, 48109.
authors.forename: Hongjiu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, 48109.|Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan, 48109.
authors.forename: Brandon
authors.initials: B
authors.lastname: Govindarajoo
authors.affiliation: Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, 48109.|Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan, 48109.
authors.forename: Jouko
authors.initials: J
authors.lastname: Virtanen
authors.affiliation: Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, 48109.|Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan, 48109.
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Xue
authors.affiliation: Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, 48109.|Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan, 48109.
authors.forename: Hong-Bin
authors.initials: HB
authors.lastname: Shen
authors.affiliation: Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, 48109. zhng@umich.edu.|Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan, 48109. zhng@umich.edu.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D001419:Bacteria / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry*; D019295:Computational Biology / Q000379:methods / Q000706:statistics & numerical data*; D003198:Computer Simulation; D030562:Databases, Protein; D006801:Humans; D007391:International Cooperation; D008958:Models, Molecular; D015233:Models, Statistical; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D012984:Software
chemical_list: D001426:Bacterial Proteins
keywords: CASP11; I-TASSER; QUARK; ab initio folding; protein structure prediction