Atomic model of the recognition site of the American cockroach pheromone receptor.

All the minimum-energy conformations (MECs) of two sex pheromones of the American cockroach,Periplaneta americana, and their 11 structural analogs (seven agonists, two antagonists, and two inactive compounds) were calculated using the molecular mechanics method. The MECs of the analogs were compared with the most populated MECs of the pheromones. The MECs most common in all the ligands were assumed to represent the bioactive conformations. An atomic model complementary to the bioactive conformation of one of the pheromones, periplanone B, was constructed. The model incorporates five groups capable of forming H bonds with oxygen atoms of the ligands and a set of hydrogen atoms contributing to nonbonded interactions with the ligands. Using this model, the energies of ligand-receptor complexes were calculated. For a group of mimics, the activities predicted from the calculated energies of ligand-receptor interactions were in reasonable agreement with the experimentally observed activities. The sites of the receptor model essential for the receptor activation were specified.