Bioinformatics Vol. 19 no. 13 2003
Pages 1682-1691
© 2003 Oxford University Press
Consensus alignment for reliable framework prediction in homology modeling
1 Bioinformatics Graduate Program and 2 Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA
Received on December 16, 2002
; revised on December 27, 2002
; accepted on March 7, 2003
Motivation: Even the best sequence alignment methods frequently fail to correctly identify the framework regions for which backbones can be copied from the template into the target structure. Since the underprediction and, more significantly, the overprediction of these regions reduces the quality of the final model, it is of prime importance to attain as much as possible of the true structural alignment between target and template.
Results: We have developed an algorithm called Consensus that consistently provides a high quality alignment for comparative modeling. The method follows from a benchmark analysis of the 3D models generated by ten alignment techniques for a set of 79 homologous protein structure pairs. For 20-to-40% of the targets, these methods yield models with at least 6 Å root mean square deviation (RMSD) from the native structure. We have selected the top five performing methods, and developed a consensus algorithm to generate an improved alignment. By building on the individual strength of each method, a set of criteria was implemented to remove the alignment segments that are likely to correspond to structurally dissimilar regions. The automated algorithm was validated on a different set of 48 protein pairs, resulting in 2.2 Å average RMSD for the predicted models, and only four cases in which the RMSD exceeded 3 Å. The average length of the alignments was about 75% of that found by standard structural superposition methods. The performance of Consensus was consistent from 2 to 32% target–template sequence identity, and hence it can be used for accurate prediction of framework regions in homology modeling.
Availability: The algorithm is available as a server at http://structure.bu.edu/cgi-bin/consensus/consensus.cgi
Contact: ccamacho{at}bu.edu
* To whom correspondence should be addressed.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  N. Fernandez-Fuentes, B. K. Rai, C. J. Madrid-Aliste, J. Eduardo Fajardo, and A. Fiser Comparative protein structure modeling by combining multiple templates and optimizing sequence-to-structure alignments Bioinformatics, October 1, 2007; 23(19): 2558 - 2565. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Fernandez-Fuentes, C. J. Madrid-Aliste, B. K. Rai, J. E. Fajardo, and A. Fiser M4T: a comparative protein structure modeling server Nucleic Acids Res., July 13, 2007; 35(suppl_2): W363 - W368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. K. Rai, C. J. Madrid-Aliste, J. E. Fajardo, and A. Fiser MMM: a sequence-to-structure alignment protocol Bioinformatics, November 1, 2006; 22(21): 2691 - 2692. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Chivian and D. Baker Homology modeling using parametric alignment ensemble generation with consensus and energy-based model selection Nucleic Acids Res., October 18, 2006; 34(17): e112 - e112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Nabhan and P. Ribeiro The 19 S Proteasomal Subunit POH1 Contributes to the Regulation of c-Jun Ubiquitination, Stability, and Subcellular Localization J. Biol. Chem., June 9, 2006; 281(23): 16099 - 16107. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Kozakov, K. H. Clodfelter, S. Vajda, and C. J. Camacho Optimal Clustering for Detecting Near-Native Conformations in Protein Docking Biophys. J., August 1, 2005; 89(2): 867 - 875. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Prasad, S. Vajda, and C. J. Camacho Consensus alignment server for reliable comparative modeling with distant templates Nucleic Acids Res., July 1, 2004; 32(suppl_2): W50 - W54. [Abstract] [Full Text] [PDF]
|
|