Pairwise alignment incorporating dipeptide covariation.
BACKGROUND
Standard algorithms for pairwise protein sequence alignment make the simplifying assumption that amino acid substitutions at neighboring sites are uncorrelated. This assumption allows implementation of fast algorithms for pairwise sequence alignment, but it ignores information that could conceivably increase the power of remote homolog detection. We examine the validity of this assumption by constructing extended substitution matrices that encapsulate the observed correlations between neighboring sites, by developing an efficient and rigorous algorithm for pairwise protein sequence alignment that incorporates these local substitution correlations and by assessing the ability of this algorithm to detect remote homologies.


RESULTS
Our analysis indicates that local correlations between substitutions are not strong on the average. Furthermore, incorporating local substitution correlations into pairwise alignment did not lead to a statistically significant improvement in remote homology detection. Therefore, the standard assumption that individual residues within protein sequences evolve independently of neighboring positions appears to be an efficient and appropriate approximation.
Crooks
Gavin E
GE
Department of Plant and Microbial Biology 111 Koshland Hall #3102 University of California, Berkeley, CA 94720-3102, USA. gec@compbio.berkeley.edu
Green
Richard E
RE
Brenner
Steven E
SE
D000465:Algorithms; D000595:Amino Acid Sequence; D004151:Dipeptides / Q000032:analysis / Q000737:chemistry*; D008969:Molecular Sequence Data; D011506:Proteins / Q000032:analysis / Q000737:chemistry*; D016415:Sequence Alignment / Q000379:methods*; D020539:Sequence Analysis, Protein / Q000379:methods*; D012984:Software
D004151:Dipeptides; D011506:Proteins