Computational Insights into Chromene/pyran Derivatives: Molecular Docking, ADMET Studies, DFT Calculations, and MD Simulations as Promising Candidates for Parkinson's Disease

Abstract

AbstractParkinson′s disease (PD) is a neurodegenerative condition characterized by both motor and non‐motor symptoms. Although PD is commonly associated with a decline of dopaminergic neurons in the substantia nigra, other diagnostic criteria and biomarkers also exist. In the search for novel therapeutic agents, chromene and pyran derivatives have shown potential due to their diverse pharmacological activities. This study utilizes a comprehensive computational approach to investigate the viability of chromene/pyran compounds as potential treatments for PD. The drug‐likeness characteristics of these molecules were analyzed using ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) studies. Molecular docking was performed against PDB ID: 2V5Z. The best three molecules chosen were compound 7, compound 24, and compound 67 have a binding energy of −6.7, −8.6, and −10.9 kcal/mol. Molecules demonstrating positive blood‐brain barrier permeability, good solubility, and favorable binding affinity were further evaluated using Density Functional Theory (DFT) calculations and Molecular Dynamics (MD) simulations to assess their electronic structure and stability. DFT calculations indicated that molecule 82 has a dipole moment of 15.70 D. RMSD and RMSF results confirmed the stability of the complexes over a 100 ns simulation, with a maximum of 3 hydrogen bonds formed.