Natural compound targeting BDNF V66M variant: insights from in silico docking and molecular analysis

Brain-Derived Neurotrophic Factor ( BDNF ) is a neurotrophin gene family gene that encodes proteins vital for the growth, maintenance, and survival of neurons in the nervous system. The study aimed to screen natural compounds against BDNF variant (V66M), which affects memory, cognition, and mood regulation. BDNF variant (V66M) as a target structure was selected, and Vitamin D, Curcumin, Vitamin C, and Quercetin as ligands structures were taken from PubChem database. Multiple tools like AUTODOCK VINA, BIOVIA discovery studio, PyMOL, CB-dock, IMOD server, Swiss ADEMT, and Swiss predict ligands target were used to analyze binding energy, interaction, stability, toxicity, and visualize BDNF -ligand complexes. Compounds Vitamin D3, Curcumin, Vitamin C, and Quercetin with binding energies values of − 5.5, − 6.1, − 4.5, and − 6.7 kj/mol, respectively, were selected. The ligands bind to the active sites of the BDNF variant (V66M) via hydrophobic bonds, hydrogen bonds, and electrostatic interactions. Furthermore, ADMET analysis of the ligands revealed they exhibited sound pharmacokinetic and toxicity profiles. In addition, an MD simulation study showed that the most active ligand bound favorably and dynamically to the target protein, and protein–ligand complex stability was determined. The finding of this research could provide an excellent platform for discovering and rationalizing novel drugs against stress related to BDNF (V66M). Docking, preclinical drug testing and MD simulation results suggest Quercetin as a more potent BDNF variant (V66M) inhibitor and forming a more structurally stable complex.