Identification of Potential Compounds from Medicinal Plants using Molecular Docking and Molecular Dynamics Simulation with SpecialReference to Autism Spectrum Disorder

INTRODUCTION/OBJECTIVE: Autism spectrum disorder (ASD) aetiology is a multifactorial concept, involving genetic susceptibility as well as environmental and neuroinflammatory mechanisms. In this context, the present study aimed to identify neuroprotective and antiinflammatory phytoconstituents of indigenous medicinal plants using molecular docking and molecular dynamics (MD) studies against key proteins involved in the pathophysiology of ASD. METHODS: A panel of ASD-associated proteins, including brain-derived neurotrophic factor (BDNF), interleukin-17 alpha (IL-17α), and indoleamine 2,3-dioxygenase-1 (IDO-1), was virtually screened. The most promising protein-ligand complexes, selected based on docking scores, were further assessed using Nanoscale Molecular Dynamics (NAMD) and Visual Molecular Dynamics (VMD) to evaluate their conformational stability. Using SwissADME and additional ADMET tools, the pharmacokinetic properties and possible toxicity of the lead compounds were predicted. RESULTS: Piperine was found to possess the highest affinity to BDNF (-8.62 kcal mol⁸¹), IDO-1 (-8.75 kcal mol⁸¹), and IL-17α (-9.18 kcal mol⁸¹). The MD simulations indicated no unstable interactions, and the BDNF-piperine complex (PDB ID: 1BND) had the lowest root-mean-square deviation (RMSD) of 0.306 ± 0.203 nm. ADMET and SwissADME models indicated that piperine's bioavailability was favourable and its predicted toxicity was low. DISCUSSION: The strong binding affinities and stable MD trajectories indicate that piperine may inhibit neuroinflammatory signaling pathways involved in ASD. Its pharmacokinetic properties also solidify its lead compound candidature. However, such computational understanding requires further investigation to support therapeutic efficacy and safety. CONCLUSION: The findings suggested that piperine may be a promising natural phytochemicalbased therapeutic in treating neuropsychiatric disorders, including ASD, by targeting neuroinflammatory pathways.