Molecular mechanisms of caramel-like odorant-olfactory receptor interactions based on a computational chemistry approach

[Display omitted] •Interaction mechanisms of 18 caramel-like odorant-receptor complexes were studied.•A new strategy for caramel-like odorants screening was established.•Binding energies were positively related to caramel-like odorants’ molecular weight.•H-bond and pi-pi stacking were the key forces for stabilizing caramel-like odorants.•The receptors activated by caramel-like odorants were different or even not-unique. Molecular mechanisms of caramel-like odorant-olfactory receptor interactions were investigated based on molecular docking and molecular dynamics simulations. The transmembrane regions TM-3, TM-5 and TM-6 of receptors were main contributors of amino acid residues in the docking. Molecular docking results showed that hydrogen bonding and pi-pi stacking were the key forces for the stabilization of caramel-like odorants. The binding energies were positively correlated with the molecular weight of caramel-like odorants. Residues Asn155 (84%, OR2W1), Asn206 (86%, OR8D1), Ser155 (77%, OR8D1), Asp179 (87%, OR5M3), Val182 (84%, OR2J2) and Tyr260 (94%, OR2J2) with high frequencies played an important role in the complexes formation. Odorants 4-hydroxy-5-methylfuran-3(2H)-one (16#) and methylglyoxal (128#) were screened by molecular field-based similarity analysis, which tended to bind to the receptors OR1G1 and OR52H1 respectively, resulting a caramel-like aroma perception. The obtained results are useful for better understanding the perception of caramel-like odorants and their high-throughput screening.