Homology modeling and ligand docking of human brain-derived neurotrophic factor (BDNF)

Abstract

Brain-derived neurotrophic factor, a protein belonging to the neurotrophin family, interacts with receptors known as TrkB and p75NTR that are present in the nervous system. A BDNF gene is responsible for the plasticity of glutamate, and GABA synapses and also influences the differentiation of neurons and impacts serotonergic and dopaminergic neurotransmission. The present study presents strcuctural bioinformatics of the BDNF protein, assessing structural and functional consequences by predicting its sequence analysis and structural modeling. The results found that BDNF is negatively charged, and non-polar with a hydrophilic and soluble GRAVY score of -0.456 and is generally unstable, based on its physiochemical attributes. The prevalence of α-helices relative to β-type structures highlights significant structural characteristics associated with the functional BDNF elements. The selected protein was studied using in-silico tools for 3D structure prediction as a potential target for protein-ligand docking analysis. PyRx tool findings revealed that IND24, Congo red, Neoamphimedine, Amphimedine, Deoxyamphimedine, and Emetine had the highest docking scores and the most stable interactions with the protein model. Based on these findings, the selected protein emerges as a promising target for protein-ligand docking, a computational method for identifying potential drug molecules. Through protein-ligand docking, researchers aim to discover new therapeutic candidates that can modulate the function of the selected protein and potentially impact associated brain diseases.