Introduction: Introduction:
Aptamers are short, single-stranded DNA or RNA (ssDNA or ssRNA) molecules that are used as drugs and drug carriers. DNA methylation is a post-replication epigenetic modification. DNA methyltransferases (DNMT) play a major role in regulating gene expression and producing and maintaining DNA methylation patterns. DNA methyltransferases are overexpressed in many types of tumors. For this reason, DNA methyltransferase inhibitor act on tumor cells as an anticancer agent. In this study, the anticancer potential of TFRA4 aptamer by inhibiting DNA methyltransferases was targeted.
Methods: Methods:
First, we downloaded the appropriate protein code of DNA methyltransferases from the PDB website. DISCOVERY software was used to start the changes on the protein. Our protein code was 4wxx with a resolution of 2.62A. To make the necessary changes in this protein, the main chain of the protein was obtained and non-protein parts such as co-crystal and water molecules were deleted then the final protein in PDB format was saved. In the next step, to prepare the LP complex (ligand + protein) we used the docking approach. Finally, by the aptamer database site, we found complete information on the aptamer ligand.
Results: Results:
TFRA4 aptamer with 14 nucleotides in length, molecular weight: 4338 g/mole, extinction coefficient: 146 L/(mole•cm), and GC content: 71.43% can bind to DNA methyltransferases. After complex analysis, we identified the Hbonds which including A:LYS697:NZ - :DT4:OP1, A:TYR976:OH - :DC12:OP1, A:ARG1311:NH1 - :DC9:OP2, A:ARG1311:NH1 - :DC9:OP2, A:GLN1340:NE2 - :DC9:OP1, A:GLN1340:NE2 - :DC9:O5' and DC5:N4 – A:GLU704:OE1
Conclusion: Conclusion:
Finally, The TRF4 aptamer showed good inhibitory potential with a docking score of -230.37 and 7 Hbonds in the binding site of DNA methyltransferases.
Keywords: DNA methyltransferases, LP complex, Docking approach, TFRA4 aptamer, 4WXX