Abstract
To improve the prediction accuracy in the regime where template alignment quality is poor, an updated version of TASSER_2.0, namely TASSER_WT, was developed. TASSER_WT incorporates more accurate contact restraints from a new method, COMBCON. COMBCON uses confidence-weighted contacts from PROSPECTOR_3.5, the latest version, PROSPECTOR_4, and a new local structural fragment-based threading algorithm, STITCH, implemented in two variants depending on expected fragment prediction accuracy. TASSER_WT is tested on 622 Hard proteins, the most difficult targets (incorrect alignments and/or templates and incorrect side-chain contact restraints) in a comprehensive benchmark of 2591 nonhomologous, single domain proteins ≤ 200 residues that cover the PDB at 35% pairwise sequence identity. For 454 of 622 Hard targets, COMBCON provides contact restraints with higher accuracy and number of contacts per residue. As contact coverage with confidence weight ≥ 3 (F(wt ≥ 3)(cov)) increases, the more improved are TASSER_WT models. When F(wt ≥ 3)(cov) > 1.0 and > 0.4, the average root mean-square deviation of TASSER_WT (TASSER_2.0) models is 4.11 Å (6.72 Å) and 5.03 Å (6.40 Å), respectively. Regarding a structure prediction as successful when a model has a TM-score to the native structure ≥ 0.4, when F(wt ≥ 3)(cov) > 1.0 and > 0.4, the success rate of TASSER_WT (TASSER_2.0) is 98.8% (76.2%) and 93.7% (81.1%), respectively.