Remarkably Strong T-Shaped Interactions between Aromatic Amino Acids and Adenine: Their Increase upon Nucleobase Methylation and a Comparison to Stacking.

T-shaped geometries and interaction energies between select DNA nucleobases (adenine or 3-methyladenine) and all aromatic amino acids (histidine, phenylalanine, tyrosine, or tryptophan) were examined using BSSE-corrected MP2/6-31G*(0.25) potential energy surface scans, which determined the preferred nucleobase (face)-amino acid (edge) and nucleobase (edge)-amino acid (face) interactions. The energies of dimers with the strongest interactions were further studied at the CCSD(T)/CBS level of theory, which suggests that the T-shaped interactions in adenine dimers are very strong (up to -35 kJ mol(-1)). Nucleobase methylation to form a cationic damaged base (3-methyladenine) plays a large role in the relative monomer orientations and magnitude of the interactions, which increase by 17-125%. Most importantly, this study is the first to compare the stacking and T-shaped interactions between all aromatic amino acids and select (natural and damaged) DNA nucleobases where the differences between stacking and T-shaped interactions at the CCSD(T)/CBS level are small. Therefore, our results indicate that T-shaped interactions cannot be ignored when studying biological processes, and this manuscript discusses the importance of these interactions in the context of DNA repair.