Published online 14 April 2005
Article |
Detecting DNA-binding helix–turn–helix structural motifs using sequence and structure information
European Bioinformatics Institute, Wellcome Trust Genome Campus Hinxton, Cambridge CB10 1SD, UK
*To whom correspondence should be addressed. Tel: +39 06 49910957; Fax: +39 06 4440062; Email: marial{at}ebi.ac.uk
Received December 10, 2004. Revised February 8, 2005. Accepted March 21, 2005.
In this work, we analyse the potential for using structural knowledge to improve the detection of the DNA-binding helix–turn–helix (HTH) motif from sequence. Starting from a set of DNA-binding protein structures that include a functional HTH motif and have no apparent sequence similarity to each other, two different libraries of hidden Markov models (HMMs) were built. One library included sequence models of whole DNA-binding domains, which incorporate the HTH motif, the second library included shorter models of ‘partial’ domains, representing only the fraction of the domain that corresponds to the functionally relevant HTH motif itself. The libraries were scanned against a dataset of protein sequences, some containing the HTH motifs, others not. HMM predictions were compared with the results obtained from a previously published structure-based method and subsequently combined with it. The combined method proved more effective than either of the single-featured approaches, showing that information carried by motif sequences and motif structures are to some extent complementary and can successfully be used together for the detection of DNA-binding HTHs in proteins of unknown function.