Understanding the Molecular Determinants of Capsaicin Mode of Action

Abstract

Capsaicin, the active component of chili peppers, is commonly used to add spice “heat” to food products. In topical pharmaceutical preparations, it is used as analgesic agent. It is known to elicit its pharmacological effects by binding to the transient receptor potential cation channel subfamily member 1 (TRPV1) which is also known as capsaicin receptor and vanilloid receptor 1. The recent development in electron cryo-microscopy allowed for the structural characterization of TRPV1. We used the information provided by the electron density map of TRPV1 to define and validate the capsaicin binding pocket and generate a reliable pose. The essential amino acid residues that are affecting the ion channel affinity to capsaicinoids were identified by extensive exploration of multiple docking poses of capsaicin and capsaicin-like compounds. TRPV1 structure does not provide information about the active site waters, we mapped the potential waters using thermodynamic studies.