Example profile logo. This logo shows positions 64 to 81 of the Peptidase_C14 profile HMM from Pfam (PF00656, Pfam 27.0), produced using Skylign. The profile HMM was constructed using hmmbuild (default parameters) from HMMER 3.1 on the Pfam seed alignment. One of the active sites of this Caspase domain is found at position 75. This site is invariant in active peptidases, but not in this profile HMM. This is the result of two forces: (1) the Pfam alignment includes non-peptidase homologs, which do not contain a Histidine at this position, and (2) HMMER intentionally drives down the information content per position (using an approach called entropy weighting ) to increase sensitivity to remote homologs.