Ab initio protein structure prediction using chunk-TASSER

¹ Georgia Institute of Technology

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

Submitted on March 30, 2007
Revised on May 2, 2007
Accepted on 9 May 2007

	Abstract

We have developed an ab initio protein structure prediction method called chunk-TASSER that uses ab initio folded supersecondary structure chunks of a given target as well as threading templates for obtaining contact potentials and distance restraints. The predicted chunks, selected on the basis of a new fragment comparison method, are folded by a fragment insertion method. Full-length models are built and refined by the TASSER methodology, which searches conformational space via parallel hyperbolic Monte Carlo. We employ an optimized reduced force field that includes knowledge-based statistical potentials and restraints derived from the chunks as well as threading templates. The method is tested on a dataset of 425 hard target proteins 250 amino acids (AA) in length. The average TM-scores of the best of top five models per target are 0.266, 0.336 and 0.362 by the threading algorithm SP³ , original TASSER and chunk-TASSER respectively. For a subset of 80 proteins with predicted -helix content 50%, these averages are 0.284, 0.356 and 0.403 respectively. The percentages of proteins with the best of top five models having TM-score 0.4 (a statistically significant threshold for structural similarity) are 3.76%, 20.94% and 28.94% by SP³ , TASSER and chunk-TASSER respectively overall, while for the subset of 80 predominantly helical proteins, these percentages are 2.50%, 23.75% and 41.25%. Thus, chunk-TASSER shows a significant improvement over TASSER for modeling hard targets where no good template can be identified. We also tested chunk-TASSER on 21 medium/hard targets less than 200 AA long from CASP7. Chunk-TASSER is about 11% (10%) better than TASSER for the total TM-score of the first (best of top five) models. Chunk-TASSER is fully automated and can be used in proteome scale protein structure prediction.

Key Words: Ab initio structure prediction, SP3, TASSER

This article has been cited by other articles:

				S. Y. Lee and J. Skolnick Benchmarking of TASSER_2.0: An Improved Protein Structure Prediction Algorithm with More Accurate Predicted Contact Restraints Biophys. J., August 15, 2008; 95(4): 1956 - 1964. [Abstract] [Full Text] [PDF]

				B. Shen, J. Bai, and M. Vihinen Physicochemical feature-based classification of amino acid mutations Protein Eng. Des. Sel., January 1, 2008; 21(1): 37 - 44. [Abstract] [Full Text] [PDF]