Prediction of oligopeptide conformations via deterministic global optimization

A deterministic global optimization method is described for identifying the global minimum potential energy conformation of oligopeptides. The ECEPP/3 detailed potential energy model is utilized for describing the energetics of the atomic interactions posed in the space of the peptide dihedral angles. Based on previous work on the microcluster and molecular structure determination [21, 22, 23, 24], a procedure for deriving convex lower bounding functions for the total potential energy function is developed. A procedure that allows the exclusion of domains of the (phi, psi) space based on the analysis of experimentally determined native protein structures is presented. The reduced disjoint sub-domains are appropriately combined thus defining the starting regions for the search. The proposed approach provides valuable information on (i) the global minimum potential energy conformation, (ii) upper and lower bounds of the global minimum energy structure and (iii) low energy conformers dose to the global minimum one. The proposed approach is illustrated with Ac-Ala(4)-Pro-NHMe, Met-enkephalin, Leu-enkephalin, and Decaglycine.