Title:Molecular Docking and Dynamics Simulation Analysis of Thymoquinone and Thymol Compounds from Nigella sativa L. that Inhibit Cag A and Vac A Oncoprotein of Helicobacter pylori: Probable Treatment of H. pylori Infections
Volume: 17
Issue: 2
Author(s): Heena Tabassum and Iffat Zareen Ahmad*
Affiliation:
- Natural Products Laboratory, Department of Bioengineering, Integral University, Dasauli, Kursi Road, Lucknow- 226026, Uttar Pradesh,India
Keywords:
N. sativa, phytoconstituents, hepatocellular carcinoma, molecular docking, simulation, H. pylori.
Abstract: Background: Helicobacter pylori infection is accountable for most of the peptic ulcer and
intestinal cancers. Due to the uprising resistance towards H. pylori infection through the present and
common proton pump inhibitors regimens, the investigation of novel candidates is the inevitable
issue. Medicinal plants have always been a source of lead compounds for drug discovery. The research
of the related effective enzymes linked with this gram-negative bacterium is critical for the
discovery of novel drug targets.
Objective: The aim of the study is to identify the best candidate to evaluate the inhibitory effect of
thymoquinone and thymol against H. pylori oncoproteins, Cag A and Vac A in comparison to the
standard drug, metronidazole by using a computational approach.
Materials and Methods: The targeted oncoproteins, Cag A and Vac A were retrieved from RCSB
PDB. Lipinski’s rule and ADMET toxicity profiling were carried out on the phytoconstituents of the
N. sativa. The two compounds of N. sativa were further analyzed by molecular docking and MD
simulation studies. The reported phytoconstituents, thymoquinone and thymol present in N. sativa
were docked with H. pylori Cag A and Vac A oncoproteins. Structures of ligands were prepared
using ChemDraw Ultra 10 software and then changed into their 3D PDB structures using Molinspiration
followed by energy minimization by using software Discovery Studio client 2.5.
Results: The docking results revealed the promising inhibitory potential of thymoquinone against
Cag A and Vac A with docking energy of -5.81 kcal/mole and -3.61kcal/mole, respectively. On the
contrary, the inhibitory potential of thymol against Cag A and Vac A in terms of docking energy
was -5.37 kcal/mole and -3.94kcal/mole as compared to the standard drug, metronidazole having
docking energy of -4.87 kcal/mole and -3.20 kcal/mole, respectively. Further, molecular dynamic
simulations were conducted for 5ns for optimization, flexibility prediction, and determination of
folded Cag A and Vac A oncoproteins stability. The Cag A and Vac A oncoproteins-TQ complexes
were found to be quite stable with the root mean square deviation value of 0.2nm.
Conclusion: The computational approaches suggested that thymoquinone and thymol may play an
effective pharmacological role to treat H. pylori infection. Hence, it could be summarized that the
ligands thymoquinone and thymol bound and interacted well with the proteins Cag A and Vac A as
compared to the ligand MTZ. Our study showed that all lead compounds had good interaction with
Cag A and Vac A proteins and suggested them to be a useful target to inhibit H. pylori infection.
