Abstract
In-view of the importance of protein-DNA interactions in biological processes, we extracted from the Protein Data Bank several one-to-one complexes of amino acids with nucleotides that matched certain geometric and energetic specificity criteria and investigated them using quantum chemistry methods. The CCSD(T)/CBS interaction energies were used as a benchmark to compare the performance of the MP2.5, MP2-F12, DFT-D3, and PM6-D3H4 methods.
All methods yielded good agreement with the reference values, with declining accuracy from MP2.5 to PM6-D3H4. Regardless of the site of interaction, the minima found after full optimization in implicit solvent with high dielectric constant were close to the structures experimentally detected in protein-DNA complexes.
According to DFT-SAPT analysis, the nature of noncovalent interactions strongly depends on the type of amino acid. The negatively charged sugar-phosphate backbone of DNA heavily influences the strength of interactions and must be included in the computational model, especially in the case of interactions with charged amino acids.