A computational methodology for designing and rationalizing the selection of small peptides as biomimetic receptors for cocaine is proposed. The method started by searching and filtering proteins X-ray and NMR data of biological receptor–cocaine complexes. On the basis of different cocaine zones, the amino acids involved in biological binding sites were selected as pivots to design an initial library of 768 penta-peptides. The peptides flexibility was studied determining the minimum number of conformers required to make a reliable computed binding score. The 25 highest ranked penta-peptides were selected and used as starting point to generate a 3000 hexapeptides library by inserting each of the 20 natural amino acids in all sequence positions. All structures were energy minimized and docking runs were carried out using FRED tool from OpenEye scientific.
The binding scores calculated by FRED were compared with a preliminary in vivo experimental test, using two different peptides as selective sorbent material used for cocaine in Solid Phase Extraction (SPE) technique coupled with Mass Spectrometry (MS). The simulation data were found to be in agreement with experimental laboratory results, supporting the methodology proposed in this work.