Abstract: The literature reports a large number of approaches for
measuring the similarity between protein sequences. Most of these
approaches estimate this similarity using alignment-based techniques
that do not necessarily yield biologically plausible results, for two
reasons.
First, for the case of non-alignable (i.e., not yet definitively aligned
and biologically approved) sequences such as multi-domain, circular
permutation and tandem repeat protein sequences, alignment-based
approaches do not succeed in producing biologically plausible results.
This is due to the nature of the alignment, which is based on the
matching of subsequences in equivalent positions, while non-alignable
proteins often have similar and conserved domains in non-equivalent
positions.
Second, the alignment-based approaches lead to similarity measures
that depend heavily on the parameters set by the user for the alignment
(e.g., gap penalties and substitution matrices). For easily alignable
protein sequences, it's possible to supply a suitable combination of
input parameters that allows such an approach to yield biologically
plausible results. However, for difficult-to-align protein sequences,
supplying different combinations of input parameters yields different
results. Such variable results create ambiguities and complicate the
similarity measurement task.
To overcome these drawbacks, this paper describes a novel and
effective approach for measuring the similarity between protein
sequences, called SAF for Substitution and Alignment Free. Without
resorting either to the alignment of protein sequences or to substitution
relations between amino acids, SAF is able to efficiently detect the
significant subsequences that best represent the intrinsic properties of
protein sequences, those underlying the chronological dependencies of
structural features and biochemical activities of protein sequences.
Moreover, by using a new efficient subsequence matching scheme,
SAF more efficiently handles protein sequences that contain similar
structural features with significant meaning in chronologically
non-equivalent positions. To show the effectiveness of SAF, extensive
experiments were performed on protein datasets from different
databases, and the results were compared with those obtained by
several mainstream algorithms.