Simulation of the Interactions between Troger Bases and DNA

Troger bases are a class of molecules that, due to its geometry, bind enantioselectively to DNA. Molecular dynamic simulations were performed with levorotatory isomers of proflavine and phenanthroline substituted Troger bases. Starting with the bases docked in DNA, the distortions they promote in the double helix were investigated in two possible modes: intercalation and minor groove binding. In the intercalation complexes, they presented long residence times and distorted the double helix leading to partial unwinding and to non-canonical values of some backbone angles. In the minor groove complexes, they displayed high mobility, leading to a change in the binding mode, interacting with the minor groove mainly through the diazocin bridge. The results suggested the intercalation of one substituent (with additional contacts in the minor groove) as the preferential binding mode for these Troger bases, while minor groove binding may explain the weaker binding observed for the dextrorotatory isomers.