Molecular Modelling of β Turns in a Cyclic Melanotropin

alpha-Melanocyte stimulating hormone (alpha-MSH) is a tridecapeptide which interacts with a family of G protein-coupled receptors, the melanocortin receptors, to cause its biological effects. We have modelled the low energy conformations of the alpha-MSH derivatives as part of a project to probe the receptor binding conformation of melanocortins, and also to design ligands for targeting cytotoxic drugs to MC1 receptors expressed by melanoma cells. Here we report a molecular dynamics study of beta turns in a cyclic lactam analogue [Nle(4), Asp(5), D-Phe(7), Lys(10)]alpha-MSH. The data show that it is possible for a beta turn to exist in the ring portion of this molecule which contains the melanocortin conserved sequence -His-Phe-Arg-Trp-, even though the lowest energy conformers lack a beta turn.