Porphyrin-based ligand interaction with G-quadruplex: Metal cation effects

The G-quadruplex planar-ligand complex is used to detect heavy metal cations such as Ag⁺, Cu²⁺, Pb²⁺, Hg²⁺, organic molecules, nucleic acids, and proteins. The interaction of the three planar porphyrins (L1), 5,10,15,20-tetrakis (1-ethyl-1-λ⁴-pyridine-4-yl) porphyrin (L2), and 5,10,15,20-tetrakis (1-methyl-1-λ⁴-pyridine-4-yl) porphyrin (L3), coming from the porphyrin family, with G-quadruplex obtained from human DNA telomeres in the presence of lithium, sodium, potassium, rubidium, cesium, magnesium, and calcium ions was studied by molecular dynamics simulation. When G-quadruplex containing divalent ions of magnesium and calcium interacts with L1, L2, and L3 ligands, the hydrogen bonds of the lower G-quadruplex sheet are more affected by ligands and the distance between guanines in the lower tetrad increases. In the case of G-quadruplex interactions containing monovalent ions with ligands, the hydrogen bond between the sheets does not follow a specific trend. For example, in the presence of lithium ions, the upper and middle sheets are more affected by ligands, while they are less affected by ligands in the presence of sodium. The binding pocket and the binding energy of the three ligands to the G-quadruplex were also obtained in the various systems. The results show that ligands make the G-quadruplex more stable through the penetration between the sheets and the interaction with the loops. Among the ligands mentioned, the interaction level of the ligand L2 is greater than the others. Our calculations are consistent with the previous experimental observations so that it can help to understand the molecular mechanism of porphyrin interaction and its derivatives with the G-quadruplex.