Molecular docking, dynamics simulation, DFT, MEP, PASS and ADMET approaches to methyl α-D-glucopyranoside derivatives for potential inhibitors of chikungunya virus

Molecular docking, dynamics simulation, DFT, MEP, PASS and ADMET to methyl α-D-glucopyranoside

Abstract

This study investigated the development of novel carbohydrate derivatives derived from methyl α-D-glucopyranoside and their potential applications in drug development. The derivatives of methyl α-D-glucopyranoside and the parent compound were optimized through advanced quantum mechanical methods, and density functional theory (DFT) calculations were carried out at the B3LYP level of theory with the 6-31G++ basis set to determine their thermodynamic parameters, such as Gibbs free energy, enthalpy, entropy, and dipole moment, which were subsequently calculated to understand their chemical behavior. Frontier molecular orbital (FMO), density of states (DOS), vibrational frequency (FT-IR), UV‒visible, and molecular electrostatic potential (MEP) analyses of the seven modified compounds were carried out. Molecular docking has been performed against the viral protein of chikungunya virus, which revealed the binding modes, nonbonding interactions, and binding affinities of these derivatives, shedding light on their potential antiviral activity. Compared with those of methyl α-D-glucopyranoside, all the derivatives presented increased binding affinities. A 150 ns molecular dynamics simulation was conducted to observe the behavior of the complex structure, revealing a stable conformation and binding mode in the stimulating environment of the compounds. Pharmacological and pharmacokinetic assessments, including toxicity, metabolism, and absorption, were conducted via ADMET and PASS to identify the most promising candidates for future development. ADMET analysis revealed that the derivatives have lower toxicity and improved pharmacokinetic features over those of the parent compound. This research highlights the therapeutic potential of carbohydrate-based compounds, paving the way for the development of new carbohydrate-derived drugs as potential inhibitors of the chikungunya virus.