Benchmarking of TASSER_2.0: An Improved Protein Structure Prediction Algorithm with More Accurate Predicted Contact Restraints

AbstractTo 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, which uses computationally evolved and wild-type template sequences as input. TASSER_2.0 was tested on a large-scale, benchmark set of 2591 nonhomologous, single domain proteins ≤200 residues that cover the Protein Data Bank 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 root mean-square deviation of 4.99Å compared to the 5.31Å result of TASSER. Defining a successful prediction as a model with a root mean-square deviation to native