With 15 N-terminal residues and 3 internal peptides of unspecified length, you may or may not be able to identify homologs. You don't want to compute E-values for the 4 small searches separately---almost nothing will come up as significant. You want to combine the scores from the separate searches. You can get a rough approximation by saying that the p-value for finding the same sequence from query A and query B is roughly the product of the p-values (this isn't quite right, but is probably close enough for your purposes). The E-value is just the p-value times the effective size of the database being searched. Note that the produce of E-values would have to be scaled down by the effective size of the database, so two queries hitting with E-value 1 on the same sequence is not an E-value of 1, but an E-value of 1/database size. Getting two or three hits on the same sequence with your different queries will quickly become significant, even if the individual E-values are around 100. If you know the order of the internal peptides, you can build a profile HMM for the sequence with high-probability inserts between the fragments, and use HMM tools to look for homologs. There are only 6 possible orders, so you could just try all 6. Kevin Karplus karplus at soe.ucsc.edu http://www.soe.ucsc.edu/~karplus Professor of Computer Engineering, University of California, Santa Cruz Undergraduate and Graduate Director, Bioinformatics Affiliations for identification only.