The Interaction of Small Molecules with Biomolecules

The binding of small molecules with biological targets is associated to interesting chemical and biologicalproperties of the resulting supramolecular systems. We have recently reported on the synthesis andcharacterization of cationic first row transition metal complexes and the study of their DNA bindingproperties, in aqueous solutions at neutral pH, essentially investigated by viscosimetry and spectroscopictechniques such as circular dichroism, absorption and fluorescence in the UV-visible wavelength range. Ofcourse, such procedure cannot furnish atomic level details of the molecule-DNA interaction. ComputationalChemistry may provide support for the interpretation of experimental data on an atomistic level (Fig.1). Forexample, we have recently shown that Molecular Dynamics (MD) simulations, followed by quantummechanics/molecular mechanics (QM/MM) calculation, provided detailed structural informations andbinding energies of the complexes between nickel(II), copper(II), zinc(II) metallointercalators with nucleicacids in the canonical B conformation [1]. We are presently applying such complementary experimental andcomputational approach to the interaction of small molecules with G-quadruplex (G4) DNA. The latter is anon-canonical conformation recently observed in human cells [2], and it has been proposed as a target for anovel class of anticancer drugs. Recently we have performed MD simulation to have an insight into themolecular recognition process of small organic ligands and other biological targets, such as mRNA andproteins [3].