Objective: The study aimed to evaluate the Withaferin-A against the drug target α-amylase, revealing its plausible mode of action and molecular-level interactions essential for this specific target inhibitory potential computational approach.
Materials and methods: In this scenario, we used computational methods, including docking, molecular dynamics simulation, and model-building simulations, to elucidate the atomic-level details responsible for the inhibitory potential of Withaferin-A derived from W. somnifera. The studio visualizer software was used for the visualization of ligands, structures of the receptor, bond length, and rendering of the image. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics of phytochemicals were investigated. Crystal structure of protein receptors and ligands were generated. Semi-flexible docking was done using Autodock software. Docking was performed using the Lamarckian Genetic Algorithm (LGA). Molecular descriptors were evaluated, and the pharmacological properties of the phytochemicals were explored. Molecular dynamic simulations were analyzed at the atomic level. All the simulations were conducted under the same temperature, pressure, and volume circumstances over the simulated time scale.
Results: Withaferin-A has shown a strong binding affinity towards α-amylase as demonstrated with -9.79 Kcal/mol with 66.61 estimated nanomolecular IC50 value for plausible anti-obesity activity. Molecular-level relationships and knowledge obtained from this study indicate solid interactions with TYR59, ASP197, and HIS299 residues which are of high importance for future works related to computational screening of target-specific α-amylase inhibitors. The results from the analysis have revealed potential molecular-level interactions useful for further designing/discovering novel α-amylase inhibitors.
Conclusions: The framework of the studied phytochemicals enables the rapid development of subsequent modifications that could result in more lead-like compounds with better inhibitory efficacy and selectivity for α-amylase.