Background Genome-sequencing projects are currently producing an enormous amount of new sequences and cause the rapid increasing of protein sequence databases. The unsupervised classification of these data into functional groups or families, clustering, has become one of the principal research objectives in structural and functional genomics. Computer programs to automatically and accurately classify sequences into families become a necessity. A significant number of methods have addressed the clustering of protein sequences and most of them can be categorized in three major groups: hierarchical, graph-based and partitioning methods. Among the various sequence clustering methods in literature, hierarchical and graph-based approaches have been widely used. Although partitioning clustering techniques are extremely used in other fields, few applications have been found in the field of protein sequence clustering. It is not fully demonstrated if partitioning methods can be applied to protein sequence data and if these methods can be efficient compared to the published clustering methods. Methods We developed four partitioning clustering approaches using Smith-Waterman local-alignment algorithm to determine pair-wise similarities of sequences. Four different sets of protein sequences were used as evaluation data sets for the proposed methods. Results We show that these methods outperform several other published clustering methods in terms of correctly predicting a classifier and especially in terms of the correctness of the provided prediction. The software is available to academic users from the authors upon request.
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