Comparing Dimerization Free Energies and Binding Modes of Small Aromatic Molecules with Different Force Fields

Area of Science:

• Computational Chemistry
• Molecular Dynamics
• Supramolecular Chemistry

Background:

• Dimerization free energies quantify molecular interaction strength.
• Experimental determination is challenging for small molecules due to system size and subtle energy differences.
• Computational methods are often necessary for accurate calculations.

Purpose of the Study:

• To calculate the dimerization free energy of small aromatic rings using computational methods.
• To compare the performance of three popular atomistic force field models (G54a7, CHARMM36, OPLS).
• To investigate the impact of molecule size on force field accuracy for stacking interactions.

Main Methods:

• Molecular dynamics (MD) simulations.
• Metadynamics simulations for free energy calculations.
• Comparison of G54a7, CHARMM36, and OPLS force field models.

Main Results:

• All tested force fields produced similar dimerization free energy profiles for small aromatic rings.
• Force field dependent stacking preferences emerged for larger molecules like pyrene and tetracene.
• Deviations increased with molecular size, highlighting the importance of force field selection for larger systems.

Conclusions:

• Force field choice has minimal impact on dimerization free energy profiles for small aromatic rings.
• Careful force field selection is crucial for accurately modeling stacking interactions in larger aromatic systems.
• Results offer a foundation for using computational tools in drug design and supramolecular assembly involving aromatic moieties.