Glycogen Synthase Kinase-3 Beta Protein Inhibition by Selected Phytocompounds in Silico

Abstract

Objectives: Bioactive phytocompounds are a rich source of chemopreventive substance. In the present investigation, docking study was performed for the selected bioactive phytocompounds such as oleanolic acid, ecdysterone, betaine, stigmasterol acetate, and cinnamic acid to evaluate their affinity to glycogen synthase kinase-3 beta (GSK-3β) protein, a wound-healing biomarker. 2-chloro-5-[4-(3-chloro-phenyl)-2, 5-dioxo-2,5-dihydro-1h-pyrrol-3-ylamino]-benzoic acid was used as an inhibitor for GSK-3β with minimum binding energy (−31.5 kcal/mol).Methods: Molecular docking study was conducted using AutoDock 4.2 version and the visualization result using Discover Studio 4.5. Results:The docking analysis ranked the selected phytocompounds that have high theoretical scores to bind to the proteins. The binding mode of the phytocompounds that bound to all the target proteins with high affinity was studied. The simulation demonstrated that the protein-ligand complex stabilized by multiple hydrogen bonds (H-bonds) was preferentially formed at the catalytic site. The results highlighted in this study reveals that among the selected lead phytocompounds that docked into the active site of GSK-3β, ecdysterone showed acceptable 6 H-bond interactions with residues LYS85, TYR134, ARG141, GLN185, ASP200, PRO136 when compared to the reference compound with 5 H-bond interactions. Conclusion:Thus, based on the docking score ecdysterone could be considered as a novel compounds that can be used for experimental studies for the inhibition of GSK-3β kinase. These results can be helpful for further design of novel GSK-3β inhibitors.

Design and fabrication of electrospun Morinda citrifolia-based nanofibrous scaffold as skin wound dressing material: in vitro and in silico analysis

“…Also, the GSK3β protein plays a vital role in several diseases including diabetes, cancer, cardiac disease, Alzheimer's disease, etc. Hence, it is considered to be one of the potential therapeutic targets for drug discovery studies [25]. In our study, the docking analysis results suggest that the phytochemical compounds present in MC can act as a potent drug molecule against the GSK3β-protein involved in the treatment of wound healing.…”

Energy-Based Pharmacophore Modeling, Virtual Screening, and Molecular Dynamics to Identify Potential Inhibitors for Glycogen Synthase Kinase 3 Beta

“…Due to this and also an increased observation of sensitization in patients treated with sulfathiazole, there is a necessity for finding a new drug [36]. Phytocompounds from plants are used to treat various diseases and showed fewer side effects [37]. In this study, the wound healing phytocompound entagenic acid, lupeol, and oleanolic acid are docked with the receptor GSK3β and compared with standard drugs nitrofurazone and sulfathiazole to assess the comparative wound healing potency.…”

Molecular Docking Studies on Thiadiazole Derivatives as Protein Kinase Inhibitors

“…The basic structure of thiadiazole was got from pubmed database. The ligand structures were constructed using the splinter dictionary of Maestro 9.4 (Schrodinger, LLC) using the Optimized Potentials for Liquid Simulations-All Atom (OPLS-AA) force field [7] with the steepest descent followed by curtailed Newton conjugate gradient protocol. Partial atomic charges were computed using the OPLS-AA force field [6].…”

“…In that 6 sites where found active (1 for ligands and 5 for metals). So it was decided to keep all the amino acids in the active site of the enzyme [7].…”