Title:Computational Approach to the Discovery of Phytochemical Molecules with Therapeutic Potential Targets to the PKCZ protein
Volume: 15
Issue: 5
Author(s): Poliany G. Freitas*, Thiago C. Elias, Icaro A. Pinto, Luciano T. Costa, Paulo V.S.D. de Carvalho, Daniel de Q. Omote, Ihosvany Camps, Tati Ishikawa, Helen A. Arcuri, Susana Vinga, Arlindo L. Oliveira, Walter F.A. Junior and Nelson J.F. da Silveira
Affiliation:
- Laboratory of Molecular Modeling and Computer Simulations-MolMod-CS, Institute of Exact Sciences, Federal University of Alfenas, Alfenas,Brazil
Keywords:
HNSCC, PKCZ, molecular marker, euphorbia tirucalli, homology modeling, molecular docking, molecular dynamics.
Abstract: Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most
common malignancies in humans and the average 5-year survival rate is one of the lowest among
aggressive cancers. Protein kinase C zeta (PKCZ) is highly expressed in head and neck tumors, and
the inhibition of PKCZ reduces MAPK activation in five of seven head and neck tumors cell lines.
Considering the world-wide HNSCC problems, there is an urgent need to develop new drugs to
treat this disease, that present low toxicity, effective results and that are relatively inexpensive.
Methods: A unified approach involving homology modeling, docking and molecular dynamics
simulations studies on PKCZ are presented. The in silico study on this enzyme was undertaken
using 10 compounds from latex of Euphorbia tirucalli L. (aveloz).
Results: The binding free energies highlight that the main contribution in energetic terms for the
compounds-PKCZ interactions is based on van der Waals. The per-residue decomposition free
energy from the PKCZ revealed that the compounds binding were favorably stabilized by residues
Glu300, Ileu383 and Asp394. Based on the docking, Xscore and molecular dynamics results,
euphol, ß-sitosterol and taraxasterol were confirmed as the promising lead compounds.
Conclusion: The present study should therefore play a guiding role in the experimental design and
development of euphol, ß-sitosterol and taraxasterol as anticancer agents in head and neck tumors.
They are potential lead compounds, better than other ligands based on the best values of docking
and MM-PBSA energy.
