An HMM is a good way to model a domain family, but using HMMer without calibration is likely to result in poor models. You'll get better models using the SAM package with the provided target2k script for builing the multiple alignment, followed by the w0.5 script to do appropriate thinning and sequence weighting for building a superfamily-level model. If you need to end up with a HMMer model, you're still better off building the model with SAM and using sam2hmmer. If you don't pay careful attention to thinning and/or sequence weighting, then models built from the usual redundant alignments are terrible. ------------------------------------------------------------ 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 (starting Jan 2005) life member (LAB, Adventure Cycling, American Youth Hostels) Effective Cycling Instructor #218-ck (lapsed) Affiliations for identification only.