Predicting noncovalent interactions between aromatic biomolecules with London-dispersion-corrected DFT

Area of Science:

• Computational Chemistry
• Biomolecular Modeling
• Quantum Chemistry

Background:

• Accurate calculation of non-covalent interactions is crucial for understanding biomolecular systems.
• Density functional theory (DFT) methods often require significant computational resources for high accuracy.
• Dispersion forces play a vital role in the stability of supramolecular complexes.

Purpose of the Study:

• To evaluate interaction energies of hydrogen-bonded and pi-pi stacked supramolecular complexes.
• To assess the efficacy of dispersion-corrected atom-centered potentials (DCACPs) in DFT calculations.
• To investigate the binding profile of the anti-cancer agent ellipticine with nucleobases.

Main Methods:

• Kohn-Sham density functional theory framework.
• Generalized gradient approximation for exchange-correlation functional.
• Application of dispersion-corrected atom-centered potentials (DCACPs).

Main Results:

• DCACP calculations showed excellent agreement with post-Hartree-Fock methods.
• Ellipticine intercalation with nucleobases demonstrated a strong binding energy stabilization of nearly 40 kcal/mol.
• Significant changes in frontier orbitals were observed upon intercalation, indicating electronic structure alterations.

Conclusions:

• DCACPs offer a computationally efficient approach to enhance DFT accuracy for biomolecular complexes.
• The findings provide insights into the binding mechanisms of ellipticine and related compounds.
• This method facilitates more realistic condensed-phase studies of complex biological systems.