Unlocking the Therapeutic Potential of DMT’s: Molecular Modelling Insights into Nueropharmacological Mechanisms and Clinical Prospects
Letters in Applied NanoBioScience June 30, 2024 Rishabh Khare, K. Rajagopal, Srikanth Jupudi et al.
Depression affects about 5% of the global population. The monoamine-deficiency hypothesis links depression to depletion of neurotransmitters like serotonin, norepinephrine, and dopamine. Serotonin 5-HT2A receptors are abundant in brain regions involved in memory and thought. A computational study compared the hallucinogenic psychedelic 5-MeO-DMT with its non-hallucinogenic analog 6-MeO-DMT for binding to the 5-HT2A receptor. Molecular docking using Schrodinger's Suite 2020-1 gave XP gscores of -8.01 kcal/mol for 5-MeO-DMT and -7.43 kcal/mol for 6-MeO-DMT. MM-GBSA binding free energies were -39.20 kcal/mol for 5-MeO-DMT and 52.41 kcal/mol for 6-MeO-DMT, with 6-MeO-DMT showing superior scores. Additional computational analyses included radius of gyration, molecular surface area, solvent-accessible surface area, and polar surface area.