Porphyrin Intercalation in G4-DNA Quadruplexes by Molecular Dynamics Simulations

We investigated the intercalation of a porphyrin derivative (TMPyP) between guanine tetrads (G4-tetrads, G4t’s) in 4-stranded G4-DNA oligomers by classical molecular dynamics simulations. Contrary to experimental evidence on very short oligomers that contain stabilizing cations, we find that TMPyP can stack with the G4-tetrads in the absence of interplane cations. A high TMPyP/G4t stoichiometric ratio of 1/2 induces strong deformations of the G4-quadruplexes. A lower ratio of 1/8 is better compatible with the helical conformation. When a TMPyP is accommodated between two tetrads, the stacking distance between the intercalated molecule and a G4-tetrad is ∼4.3−4.7 Å. We find that the possibility of regular TMPyP intercalation depends on the length of the quadruplex, on the stoichiometric ratio and on the edge termination motif.