Molecular Docking Study of Binding of Perylene Di-imide to a Bio Molecular Human Telomeric G-quadruplex

Abstract

Human telomeres are comprised of d(TTAGGG) repeats involved in the formation of G-quadruplex DNA structures. Ligands stabilizing these G-quadruplex DNA structures are potential inhibitors of the cancer cell-associated enzyme telomerase. In human cells , telomerase adds multiple copies of the 5’-GGTTAG-3’ motif to the end of the G-strand of the telomere and in the majority of tumor cells it results over-expressed. Several structural studies have revealed a diversity of topologies for telomeric quadruplexes, which are sensitive to the nature of the cations present, to the flanking sequences, and probably also to concentration, as confirmed by the different conformations deposited in the Protein Data Bank (PDB). The existence   of   different polymorphism   in the DNA quadruplex and the absence of a uniquely precise binding site give rise to check docking approach . As target we have selected six different experimental models of the human telomeric sequence d[AG3(T2AG3)3] based on three G-tetrads and as ligands the   perylene  di-imide . We checked out molecular docking simulation of binding of perylene di-imide to a slected G-quadruplex using dock 6.9 to examine whether or not to reproduced the loop binding mode of perylene di-imide.

The simulation gave the two highest rank docking pose of perylene di-imide and the binding mode were external stacking on the terminal guanine tetrade and the groove binding.