Rajesh asked "What is the best program (to run locally) for pairwise comparison of protein sequences (like bl2seq[blast], water & needle [EMBOSS] )?" There is no "best" program for this purpose. Simple pairwise alignment has been implemented many times and the implementations are mostly equivalent, as the algorithm is quite simple. If you have to do many large alignments, you might want one of the implementations that is space-efficient. This tends to matter more for DNA aligners than protein aligners, and most protein sequences are relatively short. If you plan later to do something other than pairwise alignment (such as multiple alignments, profile-sequence alignment, or profile-profile alignment), you will probably find that the tool you use for that purpose can do a perfectly adequate job of pairwise alignment also. So the best tool is the one that generalizes in the direction you want to go. ------------------------------------------------------------ Kevin Karplus karplus at soe.ucsc.edu http://www.soe.ucsc.edu/~karplus Professor of Biomolecular Engineering, University of California, Santa Cruz Undergraduate and Graduate Director, Bioinformatics (Senior member, IEEE) (Board of Directors, ISCB) life member (LAB, Adventure Cycling, American Youth Hostels) Effective Cycling Instructor #218-ck (lapsed) Affiliations for identification only.