Partition of thermodynamic energies of drug-DNA complexation.

We report a computation methodology, which leads to the ability to partition the Gibb's free energy for the complexation reaction of aromatic drug molecules with DNA. Using this approach, it is now possible to calculate the absolute values of the energy contributions of various physical factors to the DNA binding process, whose summation gives a value that is reasonably close to the experimentally measured Gibb's free energy of binding. Application of the methodology to binding of various aromatic drugs with DNA provides an answer to the question "What forces are the main contributors to the stabilization of aromatic ligand-DNA complexes?"

Electrostatic contribution to the energy of binding of aromatic ligands with DNA.

The method of solution of the nonlinear Poisson-Boltzmann equation was used to calculate electrostatic energy of binding of various aromatic ligands with DNA oligomers of different length. Analysis of the electrostatic contribution was made in terms of a two-step DNA binding process: formation of the intercalation cavity and insertion of the ligand. The total electrostatic energy was also partitioned into components: the energy of atom-atom coulombic interactions and the energy of interaction with surrounding water. The results indicate that electrostatic interactions are, as a whole, unfavorable to the intercalation process and that a correct analysis of structure-energy interrelation for Ligand-DNA interactions should only be accomplished at the level of the components rather than at the level of total electrostatic energy.