Coupled-cluster interaction energies for 200-atom host-guest systems.

Area of Science:

• Computational Chemistry
• Molecular Modeling
• Quantum Chemistry

Background:

• Accurate calculation of interaction energies is crucial for understanding molecular recognition in systems like host-guest and protein-ligand complexes.
• Existing methods may struggle with the size and complexity of biological systems.

Purpose of the Study:

• To develop and validate a computational method for calculating interaction energies of large molecular systems.
• To assess the accuracy of the new method against experimental data and compare it with existing techniques.

Main Methods:

• Developed a method combining pairwise quantum-mechanical evaluation for short-range interactions with polarizable multipole treatment for many-body effects.
• Employed local coupled-cluster with singles, doubles, and perturbative triples (a specific quantum chemistry method) and extrapolation to a complete basis set limit.
• Applied the method to nine guest molecules interacting with an octa-acid host, as part of the SAMPL4 challenge.

Main Results:

• The developed method achieved an accuracy of 10 kJ/mol or better for the tested host-guest systems.
• Comparison revealed that dispersion-corrected density functional theory underestimates dispersion contributions in these systems.
• This underestimation by DFT led to differences in ligand ranking compared to the new method.

Conclusions:

• The new computational approach provides accurate interaction energies for large molecular systems.
• The method offers a significant improvement over dispersion-corrected density functional theory for evaluating dispersion interactions in host-guest systems.
• This advancement has implications for drug discovery and understanding molecular binding.