Abstract

MOLECULAR SIMULATION STUDY OF FLUORINE SUBSTITUTED CHALCONES

Suman Uraiha*, Lata Patel Choudhary and Yogesh Pounikar

Abstract

The study explores the structural and dynamic behavior of fluorinated chalcone derivatives using advanced molecular modeling techniques. Chalcones, a class of naturally occurring polyphenolic compounds, have garnered considerable attention due to their broad spectrum of pharmacological activities. Fluorine substitution on the chalcone scaffold is known to significantly influence the compound's physicochemical properties, metabolic stability, and bioactivity. In this study, a series of fluorine-substituted chalcones were designed and their interaction potential was assessed against a selected biological target using molecular docking approaches. The most promising compounds, based on binding affinity and interaction profiles, were further subjected to 100 ns molecular dynamics (MD) simulations to assess their stability, conformational flexibility, and protein-ligand interaction dynamics under physiological conditions. Key parameters such as Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), Radius of Gyration (Rg), Solvent Accessible Surface Area (SASA), and hydrogen bond occupancy were analyzed to evaluate complex stability and interaction strength. The simulation results demonstrated that fluorine substitution improved the binding affinity and maintained stable interactions with the target protein throughout the simulation period. Additionally, the substituted derivatives showed lower fluctuations and compact structural behavior, suggesting enhanced pharmacological potential. Overall, this study confirms the utility of fluorine-modified chalcones as potent lead candidates and demonstrates the effectiveness of molecular simulation techniques in early-stage drug discovery. The findings pave the way for further experimental validation and optimization of chalcone-based compounds for therapeutic applications.

Keywords: Chalcone, In silico, Molecular Simulation, Fluorine, Docking, Derivatives.