• Investigating the efficacy of vemurafenib, regorafenib, gefitinib and erlotinib on serine/threonine specific protein kinase by molecular docking method
  • ghazaleh keshavarz,1,*


  • Introduction: Serine/threonine-specific protein kinase or BRAF is a protein playing a role in regulating cell growth, signaling, cell movement, and apoptosis, and in case of mutation in the BRAF gene, there is a possibility of normal cells would turn cancerous. Mutant B-Raf proteins are involved in tumorigenesis and most are of high kinase activity known as gain of function mutations . Vemurafenib drug belongs to the category of enzyme inhibitors (kinase inhibitors) and is among the targeted cancer drugs blocking the growth of cancer by stopping a protein called BRAF. Regorafenib is a cancer drug containing the active ingredient regorafenib. It has tyrosine kinase inhibitory activity and prevents tumor growth. It is used for patients who used other cancer treatment drugs but did not recover. Gefitinib drug belongs to the group of anti-cancer drugs and by interfering with the growth of cancer cells, it slows down or stops their growth. It has an effect on a specific enzyme protein called tyrosine kinase and inhibits it. Erlotinib is one of the cancer drugs and tyrosine kinase inhibitors, interfering with the growth of cancer cells and preventing them from spreading in the body. The aim of this research is to investigate the bioinformatics inhibition of BRAF mutated proteins by a number of anti-cancer drugs and to study the effect of each of them in inhibiting BRAF protein.
  • Methods: This research has been done by descriptive-analytical method. In this study, to determine the effectiveness of the drug and the best mode of binding and energy of the drug to the, computer methods such as docking were used and the results were analyzed. The 3D structure of BRAF protein was selected from the Uniport website and downloaded in PDB format in order to perform the docking. This protein has a resolution of 6.8 Å. The three-dimensional structure of the desired drugs was selected from the PubChem website and downloaded in SDF format. Then, the 3D structure of the target protein was entered into chimera version 1.15 to prepare the protein. The desired protein has four chains, One chain was selected and the other unnecessary ones were removed from the structure, then water molecules were removed from the desired chain and hydrogen atoms and charges were added and saved in PDB format. Molecular docking was used in order to investigate the binding and interaction of the studied compounds. PyRx software was used for docking.
  • Results: According to the docking studies, we found that the vemurafenib compound has the most negative binding energy level among all the studied compounds.
  • Conclusion: vemurafenib has better affinity and RMSD effect on BRAF protein to inhibit it and prevent cancer growth.
  • Keywords: Bioinformatics, docking, vemurafenib, gefitinib, regorafenib, erlotinib, serine/threonine specific