Position specific scoring matrices (PSSMs) corresponding to aligned sequences of homologous proteins are commonly used in homology detection. A PSSM is generated on the basis of one of the homologues as a reference sequence, which is the query in the case of PSI-BLAST searches. The reference sequence is chosen arbitrarily while generating PSSMs for reverse BLAST searches. In this work we demonstrate that the use of multiple PSSMs corresponding to a given alignment and variable reference sequences is more effective than using traditional single PSSMs and hidden Markov models.