Mathematical modelling of insect neuropeptide potencies. Are quantitatively predictive models possible?

The potencies of natural adipokinetic hormones and synthetic variants have been determined in Locusta migratoria using the lipid mobilisation assay in vivo, and/or the acetate uptake assay in vitro. These data are combinations of previously published and unpublished data (a total of sixty-nine analogues), and form data sets for the construction of mathematical models of the hormone potencies. The sequence variations of amino acids in both natural and artificial adipokinetic hormone analogues were described using continuous descriptor scales z(1)', z(2)', and z(3)', each previously published scale being derived from various properties of the amino acids. By means of these z'-scales and partial least squares regression we attempted to model the potencies in Locusta migratoria of adipokinetic hormones in the two assays. Correlations (r(2) values) between predicted and actual potencies of the different peptides were up to 0.73. We discuss the potential of the partial least squares method for formulating quantitative relationships between different hormone structures and their potencies, and describe how the procedure might be used in structure-activity prediction with the construction of an optimised peptide data set.