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 These data are combination s of previously published and unpublished data (a total of sixty-nine analo gues), and form data sets for the construction of mathematical models of th e hormone potencies. The sequence variations of amino acids in both natural and artificial adipokinetic hormone analogues were described using continu ous descriptor scales z(1)', z(2)', and z(3)' each previously published sca le being derived from various properties of the amino acids. By means of th ese z'-scales and partial least squares regression we attempted to model th e potencies in Locusta migratoria of adipokinetic hormones in the two assay s. Correlations (r(2) values) between predicted and actual potencies of the different peptides were up to 0.73. We discuss the potential of the partia l least squares method for formulating quantitative relationships between d ifferent hormone structures and their potencies, and describe how the proce dure might be used in structure-activity prediction with the construction o f an optimised peptide data set. (C) 2000 Elsevier Science Ltd. All rights reserved.