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Interplay of I‐TASSER and QUARK for template‐based and ab initio protein structure prediction in CASP10
Author(s) -
Zhang Yang
Publication year - 2014
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.24341
Subject(s) - ab initio , protein structure prediction , quark , physics , computational chemistry , chemistry , computational biology , biology , protein structure , particle physics , nuclear magnetic resonance , quantum mechanics
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.