Molecular Docking, MM-GBSA, and Molecular Dynamics Approach: 5-MeO-DMT Analogues as Potential Antidepressants
Archives of Razi Institute April 4, 2023 Rajagopal, Kalirajan, Khare, Rishabh, Jupudi, Srikanth et al.
A computational study designed and screened 70,000 analogues of the psychedelic compound 5-MeO-DMT for potential antidepressant activity with fewer hallucinogenic side effects. Using molecular docking against the serotonin 1A receptor, 21 compounds showed binding scores from -11.41 to -6.53 kcal/mol; 14 of these bound more strongly than 5-MeO-DMT itself (-7.75 kcal/mol). Further analysis with MM-GBSA found 18 analogues had better binding free energy than the standard. Molecular dynamics simulations over 100 nanoseconds showed stable interactions with key receptor residues. The findings suggest several 5-MeO-DMT analogues merit further investigation as potential antidepressants.