A Perspective of Peptide Modelling

Were it not for the immense range of biological activities possessed by the peptide hormones and enzyme inhibitors, it seems likely that the molecular modelling of peptides would remain the province of a few dedicated and perhaps slightly masochistic academics. The complexity of the problem arises from the high density of functional groups found in peptides together with their inherent flexibility, which can seldom be studied satisfactorily either by such theoretical means as conformational grid search algorithms devised with ‘small molecules’ in mind, or — worse — by many experimental techniques. Spectral complexity, insolubility and solvent dependence, together with a number of other problems, make spectral analysis difficult, while the assumption that intramolecular interactions will dominate intermolecular ones cannot be made for small peptides in the solid state, and so the structural knowledge gained from X-ray data is difficult to transfer to the solution, gas phase or ‘receptor bound’ structures.