Energy hyperspace for stacking interaction in AU/AU dinucleotide step: Dispersion-corrected density functional theory...

Area of Science:

• Structural Biology
• Computational Chemistry
• Biophysics

Background:

• DNA and RNA double helices are primarily shaped by base pair stacking interactions.
• Previous studies on stacking interactions lacked geometric variation, limiting understanding of unusual roll values in RNA.
• Purine-pyrimidine steps typically exhibit small roll values due to sequence-directed features.

Purpose of the Study:

• To generate stacking energy hyperspace by modeling geometric variations (roll and slide) in base pair steps.
• To identify the most suitable quantum chemical methods for analyzing stacked base pair systems.
• To investigate the influence of sugar-phosphate backbone constraints on stacking energy contours.

Main Methods:

• Modeled base pair geometries with variations in roll and slide degrees of freedom.
• Calculated stacking energy contours using various quantum chemical methods, including dispersion corrections (DFT-D).
• Incorporated an energy penalty term for C1'-C1' distance deviations to account for RNA backbone constraints.

Main Results:

• Established reliable quantum chemical methods for stacked base pair analysis, despite computational limitations.
• All methods predicted negative roll and near-zero slide as favorable for purine-pyrimidine steps, aligning with steric clash rules.
• The DFT-D functional ωB97X-D, with a distance-based penalty, accurately predicted energy contours for AU/AU and other purine-pyrimidine steps.

Conclusions:

• The study provides a robust method for calculating stacking energies in nucleic acid double helices.
• Accounting for backbone constraints significantly improves the accuracy of energy contours, especially for specific sequences like AU/AU.
• Findings enhance the understanding of sequence-directed structural features in DNA and RNA double helices.