Conformational study of thyrotrophin-releasing hormone. I. Aspects of importance in the design of novel TRH analogues.

The solution conformations of thyrotrophin-releasing hormone (TRH), a biologically-active tripeptide, have been predicted computationally using a method which represents solution effects as a dielectric continuum surrounding the molecule throughout energy minimisation; this is described as the reaction field contribution. The predicted conformations have been compared with previous experimental and theoretical studies. Favoured conformations of TRH under other simulated conditions have also been examined, including the behaviour of the cis isomer, and have been related to possible interactions with intermediates and with specific receptors. The relevance of these predictions to the design of biologically-active analogues of TRH has been analysed.