Similarity clustering of proteins using substantive knowledge and reconstruction of evolutionary gene histories in herpesvirus

The issue of clustering proteins into homologous protein families (HPFs) has attracted considerable attention by researchers. On one side, many databases of protein families have been developed by using popular sequence alignment tools and relatively simple clustering methods followed by extensive manual curation. On the other side, more elaborate clustering approaches have been used, yet with a very limited degree of success. This paper advocates an approach to clustering protein families involving knowledge of the protein functions to adjust the parameter of similarity scale shift. One more source of external information is utilised as we proceed to reconstruct HPF evolutionary histories over an evolutionary tree; the consistency between these histories and information on gene arrangement in the genomes is used to narrow down the choice of the clustering.