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Abstract
An automated protein structure prediction algorithm, pro-sp3-Threading/ASSEmbly/Refinement
(TASSER), is described and benchmarked. Structural templates are identified using
five different scoring functions derived from the previously developed threading methods
PROSPECTOR_3 and SP(3). Top templates identified by each scoring function are combined
to derive contact and distant restraints for subsequent model refinement by short
TASSER simulations. For Medium/Hard targets (those with moderate to poor quality templates
and/or alignments), alternative template alignments are also generated by parametric
alignment and the top models selected by TASSER-QA are included in the contact and
distance restraint derivation. Then, multiple short TASSER simulations are used to
generate an ensemble of full-length models. Subsequently, the top models are selected
from the ensemble by TASSER-QA and used to derive TASSER contacts and distant restraints
for another round of full TASSER refinement. The final models are selected from both
rounds of TASSER simulations by TASSER-QA. We compare pro-sp3-TASSER with our previously
developed MetaTASSER method (enhanced with chunk-TASSER for Medium/Hard targets) on
a representative test data set of 723 proteins <250 residues in length. For the 348
proteins classified as easy targets (those templates with good alignments and global
structure similarity to the target), the cumulative TM-score of the best of top five
models by pro-sp3-TASSER shows a 2.1% improvement over MetaTASSER. For the 155/220
medium/hard targets, the improvements in TM-score are 2.8% and 2.2%, respectively.
All improvements are statistically significant. More importantly, the number of foldable
targets (those having models whose TM-score to native >0.4 in the top five clusters)
increases from 472 to 497 for all targets, and the relative increases for medium and
hard targets are 10% and 15%, respectively. A server that implements the above algorithm
is available at http://cssb.biology.gatech.edu/skolnick/webservice/pro-sp3-TASSER/.
The source code is also available upon request.