Detection of DNA-Binding Helix-Turn-Helix Motifs in Proteins Using the Pattern Dictionary Method

This chapter discusses a recent Web-based tool called “GYM” that uses pattern discovery techniques. The resulting program can be accessed from a website, which also provides additional information on HTH motifs. It reviews the most prokaryotic transcriptional regulator proteins that interact with DNA using a helix-turn-helix (HTH) motif. An algorithm based on data mining and knowledge discovery to detect HTH motifs in a given protein was designed. This algorithm assumes that a motif is constituted by the presence of a “good” combination of residues in appropriate locations of the motif. The algorithm attempts to compile such good combinations in a “pattern dictionary” by processing an aligned training set of protein sequences. The chapter explores that the GYM program has an excellent ability to predict HTH motifs. It appears to have an increased sensitivity relative to the DE program and can detect motifs with greater divergence from the training set. The GYM program also provides additional useful information about the HTH motifs in a given protein sequence. This includes a list of patterns present in the motif, all the residues from the motif that were part of some pattern in the dictionary, and for each pattern a list of proteins from the master set that shared the pattern.