title: Interplay of I-TASSER and QUARK for template-based and ab initio protein structure prediction in CASP10.
abstract: We develop and test a new pipeline in CASP10 to predict protein structures based on an interplay of I-TASSER and QUARK for both free-modeling (FM) and template-based modeling (TBM) targets. The most noteworthy observation is that sorting through the threading template pool using the QUARK-based ab initio models as probes allows the detection of distant-homology templates which might be ignored by the traditional sequence profile-based threading alignment algorithms. Further template assembly refinement by I-TASSER resulted in successful folding of two medium-sized FM targets with >150 residues. For TBM, the multiple threading alignments from LOMETS are, for the first time, incorporated into the ab initio QUARK simulations, which were further refined by I-TASSER assembly refinement. Compared with the traditional threading assembly refinement procedures, the inclusion of the threading-constrained ab initio folding models can consistently improve the quality of the full-length models as assessed by the GDT-HA and hydrogen-bonding scores. Despite the success, significant challenges still exist in domain boundary prediction and consistent folding of medium-size proteins (especially beta-proteins) for nonhomologous targets. Further developments of sensitive fold-recognition and ab initio folding methods are critical for solving these problems.
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: Yang
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D008958:Models, Molecular; D015233:Models, Statistical; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D016415:Sequence Alignment
chemical_list: D011506:Proteins
keywords: CASP10; I-TASSER; QUARK; ab initio folding; protein structure prediction; threading