On near-optimal alignments of biological sequences.

A near-optimal alignment between a pair of sequences is an alignment whose score lies within the neighborhood of the optimal score. We present an efficient method for representing all alignments whose score is within any given delta from the optimal score. The representation is a compact graph that makes it easy to impose additional biological constraints and select one desirable alignment from the large set of alignments. We study the combinatorial nature of near-optimal alignments, and define a set of "canonical" near-optimal alignments. We then show how to enumerate near-optimal alignments efficiently in order of their score, and count their number. When applied to comparisons of two distantly related proteins, near-optimal alignments reveal that the most conserved regions among the near-optimal alignments are the highly structured regions in the proteins. We also show that by counting the number of near optimal alignments as a function of the distance from the optimal score, we can select a good set of parameters that best constraints the biologically relevant alignments.