Evidence for Stabilization of DNA/RNA-Protein Complexes Arising from Nucleobase-Amino Acid Stacking and T-Shaped Interactions.

The stacking and T-shaped interactions between the natural DNA or RNA nucleobases (adenine, cytosine, guanine, thymine, uracil) and all aromatic amino acids (histidine, phenylalanine, tyrosine, tryptophan) were investigated using ab initio quantum mechanical calculations. We characterized the potential energy surface of nucleobase-amino acid dimers using the MP2/6-31G*(0.25) method. The stabilization energies in dimers with the strongest interactions were further examined at the CCSD(T)/CBS level of theory. Results at the highest level of theory possible for these systems indicate that both stacking and T-shaped interactions are very close in magnitude to biologically relevant hydrogen bonds. Additionally, T-shaped interactions are as strong, if not stronger, than the corresponding stacking interactions. Our systematic consideration of the interaction energies in 485 possible combinations of monomers shows that a variety of these contacts are essential when considering the role of aromatic amino acids in the binding of proteins to DNA or RNA. This work also illustrates how our calculated binding strengths can be used by biochemists to estimate the magnitude of these noncovalent interactions in a variety of DNA/RNA-protein active sites.