Network Pharmacology Approach to Identify the Calotropis Phytoconstituents’ Potential Epileptic Targets and Evaluation of Molecular Docking, MD Simulation, and MM‐PBSA Performance

Abstract

Epilepsy originates from unusual electrical rhythm within brain cells, causes seizures. Calotropis species have been utilized to treat a wide spectrum of ailments since antiquity. Despite chemical and biological investigations, there have been minimal studies on their anticonvulsant activity, and the molecular targets of this plant constituents are unexplored. This study was aimed at investigating the plausible epileptic targets of Calotropis phytoconstituents through network pharmacology, and to evaluate their binding strength and stability with the identified targets. In detail, 125 phytoconstituents of Calotropis plant (C. procera and C. gigantea) were assessed for their drug likeness (DL), blood‐brain‐barrier (BBB) permeability and oral bioavailability (OB). Network analysis revealed that targets PTGS2 and PPAR‐γ were ranked first and fourth, respectively, among the top ten hub genes significantly linked with antiepileptic drug targets. Additionally, docking, molecular dynamic (MD) simulation and Molecular Mechanics‐Poisson‐Boltzmann Surface Area (MM‐PBSA) were employed to validate the compound‐gene interactions. Docking studies suggested ergost‐5‐en‐3‐ol, stigmasterol and β‐sitosterol exhibit strong binding affinity and favorable interactions than co‐crystallized ligands with both the targets. Furthermore, both MD simulations and MM‐PBSA calculations substantiated the docking results. Combined data revealed Calotropis phytoconstituents ergost‐5‐en‐3‐ol, stigmasterol and β‐sitosterol might be the best inhibitors of both PTGS2 and PPAR‐γ.

Investigation on Anti‐plasmodial Agents Against wild‐type PfDHFR Through In Silico Computational Tools

“…Compound 2 was chosen for MD simulation using GROMACS 2023.4 [59] software for 100 ns and studied for simulations following the protocols adopted in the previously published literature. [60,61] Molecular dynamic (MD) simulation was used to assess the stability of compound 2 using an NVIDIA Corporation RTX A2000 graphics card running Ubuntu 22.04.3, using the GROMACS version-2023.4 package. The CHARMM27 all-atom force field was utilized to create the protein topology.…”