M-TASSER: An Algorithm for Protein Quaternary Structure Prediction
Huiling Chen 1 and Jeffrey Skolnick 2*
1 Georgia Institute of Technology
2 Georgia Tech
* To whom correspondence should be addressed. E-mail: skolnick{at}gatech.edu.
Submitted on June 4, 2007
Revised on July 23, 2007
Accepted on 18 September 2007
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Abstract |
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In a cell, it has been estimated that each protein on average interacts with roughly ten others, resulting in tens of thousands of proteins known or suspected to have interaction partners; of these, only a tiny fraction have solved protein structures. To partially address this problem, we have developed M-TASSER, a hierarchical method to predict protein quaternary structure from sequence that involves template identification by multimeric threading, followed by multimer model assembly and refinement. The final models are selected by structure clustering. M-TASSER has been tested on a benchmark set comprised of 241 dimers with weakly homologous templates and 246 without multimeric templates in the dimer library. Of the total of 207 targets predicted to interact as dimers, 165 (80%) were correctly assigned as interacting with a true positive rate of 68% and a false positive rate of 17%. The initial best template structures have an average root-mean-square-deviation (RMSD) to native of 5.3 Å, 6.7 Å and 7.4 Å for the monomer, interface, and dimer structures. The final model shows on average a RMSD improvement of 1.3 Å,1.3 Å and 1.5 Å over the initial template structure for the monomer, interface, and dimer structures, with refinement evident for 87% of the cases. Thus, we have developed a promising approach to predict full-length quaternary structure for proteins that are weakly homologous to proteins of solved quaternary structure.
Key Words:
TASSER, multimeric threading, protein complex, protein-protein interaction, quaternary structure prediction
