Accurate assessment of the potential binding mode of drugs is crucial to computer-aided drug design paradigms. It has been reported that evodiamine acts as an agonist of the vanilloid receptor Transient receptor potential vanilloid-1 (TRPV1). However, the precise interaction between evodiamine and TRPV1 was still not fully understood. In this perspective, the homology models of TRPV1 were generated using the crystal structure of the voltage-dependent shaker family K(+) channel as a template. We then performed docking and molecular dynamics simulation to gain a better understanding of the probable binding modes of evodiamine within the TRPV1 binding pocket. There are no significant interspecies differences in evodiamine binding in rat, human and rabbit TRPV1 models. Pharmacophore modeling further provided confidence for the validity of the docking studies. This study is the first to shed light on the structural determinants required for the interaction between TRPV1 and evodiamine, and gives new suggestions for the rational design of novel TRPV1 ligands.
Keywords: capsaicin; evodiamine; homology modeling; molecular docking; molecular dynamics; transient receptor potential vanilloid type 1.