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Background  Computational discovery of transcription factor binding sites (TFBS) is a challenging but important problem of bioinformatics. In this study, improvement of a Gibbs sampling based technique for TFBS discovery is attempted through an approach that is widely known, but which has never been investigated before: reduction of the effect of local optima.    Results  To alleviate the vulnerability of Gibbs sampling to local optima trapping, we propose to combine a thermodynamic method, called simulated tempering, with Gibbs sampling. The resultant algorithm, GibbsST, is then validated using synthetic data and actual promoter sequences extracted from  Saccharomyces cerevisiae . It is noteworthy that the marked improvement of the efficiency presented in this paper is attributable solely to the improvement of the search method.    Conclusion  Simulated tempering is a powerful solution for local optima problems found in pattern discovery. Extended application of simulated tempering for various bioinformatic problems is promising as a robust solution against local optima problems.

GibbsST: a Gibbs sampling method for motif discovery with enhanced resistance to local optima