Analyzing conservation patterns and its influence on identifying protein functional

Evolutionary conservation information included in position-specific scoring matrix (PSSM) has been adopted by almost all sequence-based methods for identifying protein functional sites, because all functional sites, whether in ordered or disordered proteins, are found to be conserved to some extent. However, different functional sites have different conservation patterns, some of them are linear contextual, some of them are mingled with highly variable residues, and some others seem to be conserved independently. All existing studies used the direct output of PSSM for functional sites prediction, without considering the relationship between conservation patterns of residues and the distribution of conservation scores in PSSMs. In order to demonstrate the importance of analyzing conservation patterns, three PSSM-based methods for identifying 3 kinds of functional sites have been compared. Experiment results show that, although all the methods are based on the same feature - PSSM of protein sequence, they are competent in identifying different patterns of functional sites: the PSSM-based method is competent for identifying functional site which is independently conserved; the smoothed-PSSM is competent for identifying functional site which is continuous conserved; and the masked-smoothed- PSSM based method is competent for identifying functional site which is mingled with intensively highly flexible and highly conserved residues.