Yes, the family pairwise search by Bill Grundy (now William Noble) is an interesting and fairly simple technique for trying to improve homology detection by using known relationships among sequences in the database. I've had students implement Grundy's "product of p-values" technique for our HMM-based scoring methods. In their preliminary tests, they showed that it might help, but their projects were never taken to the point where the method could be incorporated into an automatic prediction method. One problem with that method is that it treats all templates in a fold class as equally informative and does not use information from templates in competing fold classes. One can envision combining methods such as logisitic regression that could use the extra information to get better predictions. One danger is that multi-domain proteins correctly have multiple correct folds, so simple competition between fold classes is not quite the right model. ------------------------------ Kevin Karplus karplus at soe.ucsc.edu http://www.soe.ucsc.edu/~karplus Senior member, IEEE Board of Directors, ISCB (starting Jan 2005) Professor of Biomolecular Engineering, University of California, Santa Cruz Undergraduate and Graduate Director, Bioinformatics Affiliations for identification only.