Theoretical design of a specific DNA-Zinc-finger protein interaction with semi-empirical quantum chemical methods

The interactions of a zinc-finger (ZF) protein with DNA containing the specific recognition site of the ZF and with a non-specific DNA were studied with the semi-empirical quantum chemical method of PM6/Mozyme. The ZF protein (1MEY)-DNA complex structures were generated by docking calculations. The complex structures were reoptimized with the PM6/Mozyme method with implicit solvation in water. The structures were also calculated in the gas phase. The interaction enthalpies between the protein and DNA within the complexes obtained in the PM6/Mozyme with solvation optimized structures were calculated with the single-point PM6-DH2/Mozyme method (PM6 with dispersion, H-bond correction and Mozyme) with solvation. The results supported the specific and non-specific interactions in the complexes obtained from the docking experiments. The binding enthalpies of the specific and non-specific DNA binding to the protein differed significantly. The interactions between the nucleic acid strands in duplexes were also evaluated; these interactions between the base pairs were different because of the different "G…C:A…T" ratios in the DNA molecules studied. The stacking interactions between the nucleic bases were also characterized in the DNA duplexes.