In silico study of a new class of DNA fluorescent probes

Abstract

Natural fluorescence in biochemical structures can lead to unsatisfactory results in cell imaging, but this drawback can be solved using molecules which fluoresce by Excited State Intramolecular Proton Transfer (ESIPT), improving the signal-to-noise ratio. A docking study was conducted to estimate the binding free energy of 150 benzazoles and their binding mechanism (minor groove (MG) or intercalation (INT)) to the DNA and compared with dockings using the commercial probes 4’,6-Diamidino-2-phenylindole dihydrochloride (DAPI) and acridine orange (AO). Molecular Dynamics simulations were carried out with the five best-ranked compounds in physiological media. Two of these molecules have shown stronger binding energy than DAPI and AO, with one of these molecules interacting as an intercalator and the other presenting both INT and MG binding modes. The other three benzimidazoles are MG binders, where one of them presented stronger interaction than the commercial probes, and the others two demonstrated a stronger interaction than AO in docking. Molecular mechanics Poisson-Boltzmann surface area (MMPBSA) calculation was performed to estimate the binding free energy of the complex ligand-receptor. The intercalator exhibited a stronger energy than AO and DAPI in INT conformation. Two molecules presented stronger interaction than the commercial probes in both binding modes, and two molecules presented weaker interaction with the DNA than AO and DAPI. These best compounds could act as DNA probes in several diagnosis techniques.