Delta opioid receptor (DOR) is an attractive object for docking experiments, because is the target of enkephalins, which are endogenous opioid pentapeptides with DOR preferences. The aim of this study is to establish optimal fitting polynomial function for modelling of the structure-activity relationship of a series of δ-opioid selective enkephalin analogues, basing on the quantitative parameters of in vitro bioassay (efficacy, affinity and potency) and the results of the molecular docking with theoretical model of DOR (PDBe:1ozc). The relationship of efficacy with the GoldScore scoring function and with the total energy was modelled with first- to fourth-degree polynomials and surface fitted method. The polynomial surface of the third order has the best fit, assessed by method of least squares. The finding, established in this study, suggests that: (1) the third order polynomial could be successfully used for modeling of the relationship between the efficacy of δ-selective enkephalin analogues and results from docking procedure; and (2) the combination of ligand-based and structure-based approaches of virtual screening is a reliable search of effective δ-selective enkephalin candidates.
