Computational comparison of the stacking interactions between the aromatic amino acids and the natural or (cationic) methylated nucleobases

Abstract

The strongest gas-phase MP2/6-31G*(0.25) stacking energies between the aromatic amino acids and the natural or methylated nucleobases were considered. The potential energy surfaces of dimers were searched as a function of the vertical separation, angle of rotation and horizontal displacement between monomers stacked according to their centers of mass. Our calculations reveal that the stacking interactions of adducts for a given nucleobase are dependent on the methylation site (by up to 20 kJ mol(-1)), where the relative magnitudes of the interactions are determined by the dipole moments of the adducts and the proton affinities of nucleobase methylation sites. Nevertheless, the differences in the (gas-phase) stacking of methylated adducts are small compared with the differences between the stacking of the corresponding natural and methylated nucleobases. Indeed, methylation increases the stacking energy by up to 40 kJ mol(-1) (or 135%). Although immersing the dimers in different solvents decreases the gas-phase stacking energies with an increase in the polarity of the environment, base methylation still has a significant effect on the nucleobase stacking ability in solvents with large dipole moments, and, perhaps more importantly, environments that mimic enzyme active sites. Our results shed light on the workings of DNA repairs enzymes that selectively remove a wide variety of alkylated nucleobases over the natural bases.

Topology of RNA–protein nucleobase–amino acid π–π interactions and comparison to analogous DNA–protein π–π contacts

“…In these cases, the effects of amino acid charge will likely be significantly diminished. Nevertheless, previous work has shown that neutral and charged π-π interactions maintain significant strength even in more polar environments (Cauët et al 2005;Rutledge et al 2008;Churchill and Wetmore 2009). Regardless, future work should consider the effects of solvation in order to generalize our conclusions to many different RNA-protein binding environments.…”

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

“…18,21,27 Initially, C s symmetric, MP2/ 6-31G(d) optimized monomers were placed so that the nucleobase and amino acid molecular planes were parallel (stacked) or perpendicular (T-shaped) to one another. In stacked dimers involving HIS, TYR, and TRP, two relative orientations of the molecular planes were considered.…”

Rethinking the term “pi-stacking”

“…The Tschumper lab mined the Protein Data Bank for structures that exhibited phenylalanine-adenine interactions 113 and were able to categorize these into six distinct structures, all of which are stacked in a completely face-centred geometry. Many different research groups have published work supporting the idea that there is a lack of a deep energetic minimum for stacked structures between amino acids, nucleic acids, or combinations of the two; many suggest that this relative freeness allows residues to interact favourably with interaction geometries dictated by their polymeric backbones.…”