DNA base stacking: the stacked uracil/uracil and thymine/thymine minima

Area of Science:

• Computational chemistry
• Molecular modeling
• Biophysical chemistry

Background:

• Nucleobase stacking interactions are crucial for DNA/RNA structure and function.
• Understanding these interactions requires accurate computational methods.
• Uracil and thymine dimers serve as model systems for studying stacking.

Purpose of the Study:

• To investigate the potential energy surfaces of stacked uracil (U/U) and thymine (T/T) dimers.
• To explore the influence of gas phase versus continuum solvent environments on dimer stability.
• To assess the accuracy of the M06-2X/6-31+G(d) level of theory for stacking energies.

Main Methods:

• Utilized counterpoise (CP)-corrected M06-2X/6-31+G(d) calculations.
• Performed potential energy scans by rotating monomers.
• Modeled solvent effects using the polarizable continuum model (PCM) with water and 1,4-dioxane.

Main Results:

• Located five or six minima for U/U dimers and six minima for T/T dimers.
• Identified several transition states on the potential energy surfaces.
• Observed that continuum solvents tend to flatten the potential energy surfaces.
• Validated M06-2X/6-31+G(d) performance against higher-level calculations for stacking energies.

Conclusions:

• The M06-2X/6-31+G(d) method accurately describes stacking interactions in uracil and thymine dimers.
• Solvent effects significantly influence the conformational landscape of nucleobase dimers.
• This work provides a detailed energetic map of U/U and T/T stacking.