Benchmarking of TASSER_2.0: An improved protein structure prediction algorithm with more accurate predicted contact restraints

¹ Georgia Institute of Technology
² Georgia Tech

^* To whom correspondence should be addressed. E-mail: skolnick{at}gatech.edu.

Submitted on January 18, 2008
Revised on February 14, 2008
Accepted on 18 April 2008

	Abstract

To improve tertiary structure predictions of more difficult targets, the next generation of TASSER, TASSER_2.0 has been developed. TASSER_2.0 incorporates more accurate side chain contact restraint predictions from a new approach, the composite-sequence method, based on consensus restraints generated by an improved threading algorithm, PROSPECTOR_3.5 that employs computationally evolved and wild type template sequences as input. TASSER_2.0 was tested on a large-scale, benchmark set of 2,591 nonhomologous, single domain proteins 200 residues that cover the PDB at 35% pairwise sequence identity. Compared with the average fraction of accurately predicted side chain contacts of 0.37 using PROSPECTOR_3.5 with wild type template sequences, the average accuracy of the composite-sequence method increases to 0.60. The resulting TASSER_2.0 models are closer to their native structures, with an average RMSD of 4.99 Å compared to the 5.31 Å result of TASSER. Defining a successful prediction as a model with a RMSD to native <6.5 Å, the success rate of TASSER_2.0 (TASSER) for Medium targets (targets with good templates/poor alignments) is 74.3% (64.7%) and 40.8% (35.5%) for the Hard targets (incorrect templates/alignments). For Easy targets (good templates/alignments), the success rate slightly increases from 86.3% to 88.4%.

Key Words: Protein structure prediction, TASSER, TASSER_2.0, Threading, composite-sequence method, side chain contact prediction