OPUS-Dom: applying the folding-based method VECFOLD to determine protein domain boundaries.
In this article, we present a de novo method for predicting protein domain boundaries, called OPUS-Dom. The core of the method is a novel coarse-grained folding method, VECFOLD, which constructs low-resolution structural models from a target sequence by folding a chain of vectors representing the predicted secondary-structure elements. OPUS-Dom generates a large ensemble of folded structure decoys by VECFOLD and labels the domain boundaries of each decoy by a domain parsing algorithm. Consensus domain boundaries are then derived from the statistical distribution of the putative boundaries and three empirical sequence-based domain profiles. OPUS-Dom generally outperformed several state-of-the-art domain prediction algorithms over various benchmark protein sets. Even though each VECFOLD-generated structure contains large errors, collectively these structures provide a more robust delineation of domain boundaries. The success of OPUS-Dom suggests that the arrangement of protein domains is more a consequence of limited coordination patterns per domain arising from tertiary packing of secondary-structure segments, rather than sequence-specific constraints.
Wu
Yinghao
Y
Department of Bioengineering, Rice University, Houston, TX 77005, USA.
Dousis
Athanasios D
AD
Chen
Mingzhi
M
Li
Jialin
J
Ma
Jianpeng
J
D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D006801:Humans; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000737:chemistry; D020539:Sequence Analysis, Protein
D011506:Proteins; D016271:Proto-Oncogene Proteins c-myc