Interplay of I-TASSER and QUARK for template-based and ab initio protein structure prediction in CASP10

Authors

  • Yang Zhang

    Corresponding author
    1. Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan
    2. Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan
    • Correspondence to: Yang Zhang, Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109. E-mail: zhng@umich.edu

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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. Proteins 2014; 82(Suppl 2):175–187. © 2013 Wiley Periodicals, Inc.

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