Pfam domain search
With CLC Drug Discovery Workbench you can perform a search for domains in protein sequences using the Pfam database. The Pfam database [Bateman et al., 2004] at http://pfam.sanger.ac.uk/ was initially developed to aid the annotation of the C. elegans genome. The database is a large collection of multiple sequence alignments that cover 14831 protein domains and protein families as of March 2014. The database contains profile hidden Markov models (HMMs) for individual domain alignments, which can be used to quickly identify domains in protein sequences.
Many proteins have a unique combination of domains, which can be responsible for e.g. the catalytic activities of enzymes. Annotating sequences based on pairwise alignment methods by simply transferring annotation from a known protein to the unknown partner does not take domain organization into account [Galperin and Koonin, 1998]. For example, a protein may be annotated incorrectly as an enzyme if the pairwise alignment only finds a regulatory domain.
Using the Pfam Domain Search tool in CLC Drug Discovery Workbench, you can search for domains in sequence data which otherwise do not carry any annotation information. The domain search is performed using the hmmsearch tool from the HMMER3 package version 3.1b1 (http://hmmer.janelia.org/). The Pfam search tool annotates protein sequences with all domains in the Pfam database that have a significant match. It is possible to lower the significance cutoff thresholds in the hmmsearch algorithm, which will reduce the number of domain annotations. Individual domain annotations can be removed manually as described in Removing annotations.
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