The molecular basis of the antidepressant action of the magic mushroom extract, psilocin.
Biochimica et biophysica acta. Proteins and proteomics July 1, 2023 Ali Asghar Hakami Zanjani, Teresa Quynh Tram Nguyen, Luise Jacobsen et al. 6 citations
Psilocin, the active form of psilocybin in magic mushrooms, binds more strongly to the serotonin 2A receptor (5-HT2AR) than the natural hormone serotonin does. Using molecular dynamics simulations and free energy calculations, the authors show that this higher binding affinity is due to psilocin's tertiary amine group, not the different position of its hydroxyl group. The binding strength depends on the protonation states of both psilocin and a key receptor residue, aspartate 155. These molecular insights suggest design rules for developing more effective antidepressants.