in silico study of dimethyltryptamine analogues against 5-ht1b receptor: molecular docking, dynamic simulations and admet prediction

Introduction: the 5-ht1b receptor has a potential role in various psychiatric disorders such as depression, anxiety, and post-traumatic stress disorder. the objective of this study was to perform docking and molecular dynamics simulation to evaluate at atomic level the behavior of n,n-dimethyltryptamine (dmt) on 5-ht1b receptor. methods: in this study, initially, a search for dmt was performed using the pubchem database. subsequently, molecular docking was executed using autodock vina based in pyrx 0.8 with a 95% analogy. additionally, ergotamine (erg) and serotonin were used as control. then, it ran a total of 100 ns molecular dynamics simulations on 5-ht1b bound with dmt, serotonin, 112814775, and erg. finally, pharmacokinetic prediction and iv acute toxicity for analogues and dmt were performed. results: it was possible to show that 112814775 had the lowest binding energy with the receptor. in addition, 112814775 presented great conformational stability, low mobility, and stiffness compared to the control ligands: erg, serotonin, and dmt subsequent dynamic analysis. with respect to the free energy calculation, contributions such as van der waals, electrostatics, and nonpolar interactions for all systems, were highlighted. conclusion: 112814775 showed affinities with 5-ht1b receptor and evidenced notable behavior by molecular dynamic simulation according to root-mean-square deviation (rmsd), root-mean-square fluctuation (rmsf), solvent-accessible surface area (sasa), the radius of gyration, number of hydrogen bond, and free energy calculated. these results established the possible relevance of in-silico studies in search of dmt analogues against the 5-ht1b receptor, which may be associated with alterations such as depression and anxiety, and may become future study molecules for the treatment of this type of disorder.