In silico design and molecular modeling of peptidic stabilizers of G-quadruplex

Molecular modeling has a key role in drug discovery and development projects. Virtual screening methods reduce the cost of drug discovery. The role of molecular modeling methods are undeniable in development of anticancer drugs. G-quadruplexes are distinct secondary structures adopted in some guanine-rich DNA sequences. G-quadruplex forms in the promoter of oncogenes and suppresses transcriptional activity. So G-quadruplex stabilizing agents are one of the most potential anticancer agents. In the present contribution, we evaluate the interaction of DSM peptide with G-quadruplex and also design and molecular modeling of new G-quadruplex peptidic stabilizers. According to obtained results, two basic groups are the main parameter in binding to G-quadruplex. In two best designed chains, KGREIGYAK and KGREIGMYAK, lysine and arginine residues place in optimum distance and showed high affinity to G-quadruplex. These basic residues formed ionic bond with phosphate groups of DNA. Tyrosine residue formed π-π interaction with guanine ring of G4.