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  • Comparative study of the effect of Carboplatin and Capecitabine on PDL-1 protein using molecular docking method
  • Mobina Alipour,1,*
    1. The Research & Science university student


  • Introduction: Introduction: Programmed death-ligand 1 (PD-L1) also known as cluster of differentiation 274 (CD274) or B7 homolog 1 (B7-H1) is a protein that in humans is encoded by the CD274 gene. It seems that the high production of this protein causes cancer cells to escape from the body's immune system. Carboplatin is an intravenously administered platinum coordination complex and alkylating agent which is used as a chemotherapeutic agent for the treatment of various cancers, mainly ovarian, head and neck and lung cancers. Capecitabine is a carbamate ester that is cytidine in which the hydrogen at position 5 is replaced by fluorine and in which the amino group attached to position 4 is converted into its N-(penyloxy)carbonyl derivative. Capecitabine is a antineoplastic agent used in the treatment of cancers.
  • Methods: Material and method: In this study, I used the Pub Chim site at pubchem.ncbi.nlm.nih.gov, RCSB PDB www.rcsb.org to examine quercetin derivatives. Also from the software Chimera 1.17.1 and PyRx were also used. In this article, I first saved the structures of Carboplatin and Capecitabine from Pub Chim site as sdf files then I saved the 3D structure of PDL-1 protein from RCSB PDB site sa a pdb file. specifications of Carboplatin: Molecular formula: C6H12N2O4Pt Carboplatin is a second-generation platinum compound with a broad spectrum of antineoplastic properties. Carboplatin contains a platinum atom complexed with two ammonia groups and a cyclobutane-dicarboxyl residue. This agent is activated intracellularly to form reactive platinum complexes that bind to nucleophilic groups such as GC-rich sites in DNA, thereby inducing intrastrand and interstrand DNA cross-links, as well as DNA-protein cross-links. These carboplatin-induced DNA and protein effects result in apoptosis and cell growth inhibition. This agent possesses tumoricidal activity similar to that of its parent compound, cisplatin, but is more stable and less toxic. (NCI04) specifications of Capecitabine: Molecular formula: C15H22FN3O6 Capecitabine is a Nucleoside Metabolic Inhibitor. The mechanism of action of capecitabine is as a Nucleic Acid Synthesis Inhibitor. Capecitabine is a fluoropyrimidine carbamate belonging to the class of antineoplastic agents called antimetabolites. As a prodrug, capecitabine is selectively activated by tumor cells to its cytotoxic moiety, 5-fluorouracil (5-FU); subsequently, 5-FU is metabolized to two active metabolites, 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP) by both tumor cells and normal cells. FdUMP inhibits DNA synthesis and cell division by reducing normal thymidine production, while FUTP inhibits RNA and protein synthesis by competing with uridine triphosphate for incorporation into the RNA strand. (NCI04) I edited the desired protein using Chimera 1.17.1 software. The PDL-1 protein had three chains, and in this study I used only the C chain for better conformity, and the rest of the chains were deleted. Also using the software, water molecules were removed from the protein and hydrogen molecules were added to its structure. Then using PyRx software,I started molecular docking, In which the gridbox to select the appropriate docking location were as follows: Center: X:-19.963 Y:-56.048 Z:52.4653 Center: X:-19.963 Y:-56.048 Z:52.4653 Dimensions(Angstrom): X;25.0000 Y:25.0000 Z:25.0000 Dimensions(Angstrom): X;25.0000 Y:25.0000 Z:25.0000 Carboplatin Capecitabine
  • Results: Result: After performing molecular docking separately for Carboplatin and Capecitabine, the results were as shown in the tables below: Ligand Binding Affinity (Kcal/mol) Mode RMSD lower bound RMSD upper bound Profinally_2568_uff_E=536.72 -4.3 0 0.0 0.0 Profinally_2568_uff_E=536.72 -4.2 1 0.842 3.077 Profinally_2568_uff_E=536.72 -4.1 2 1.591 2.588 Profinally_2568_uff_E=536.72 -4.0 3 11.931 13.264 Profinally_2568_uff_E=536.72 -3.9 4 1.624 3.128 Profinally_2568_uff_E=536.72 -3.8 5 1.498 3.172 Profinally_2568_uff_E=536.72 -3.8 6 1.892 3.058 Profinally_2568_uff_E=536.72 -3.8 7 11.771 13.188 Profinally_2568_uff_E=536.72 -3.8 8 11.988 13.3.8 The result of Carboplatin docking Ligand Binding Affinity (Kcal/mol) Mode RMSD lower bound RMSD upper bound Profinally_60953_uff_E=341.24 -5.5 0 0.0 0.0 Profinally_60953_uff_E=341.24 -5.4 1 11.17 12.913 Profinally_60953_uff_E=341.24 -5.4 2 11.322 12.535 Profinally_60953_uff_E=341.24 -5.3 3 12.835 14.437 Profinally_60953_uff_E=341.24 -5.3 4 1.739 2.306 Profinally_60953_uff_E=341.24 -5.3 5 3.173 8.238 Profinally_60953_uff_E=341.24 -5.2 6 12.739 14.639 Profinally_60953_uff_E=341.24 -5.2 7 12.483 13.684 Profinally_60953_uff_E=341.24 -5.2 8 5.421 8.242 The result of Capecitabine docking
  • Conclusion: Conclusion: According to ducking studies, I found that conformation of Capecitabine with negative binding affinity and RMSD had a better effect on PDL-1 protein to induce apoptosis and prevent cancer cell growth.
  • Keywords: PDL-1 protein/ Cancers/ Docking molecular/ Carboplatin/ Capecitabine