Comparing dimerization free energies and binding modes of small aromatic molecules with dierent force elds

Dimerization free energies are fundamental quantities that describe the strength of interaction of dierent molecules. Obtaining accurate experimental values for small molecules and disentangling the conformations that contribute most to the binding can be extremely dicult, due to the size of the systems and the small energy dierences. In many cases, one has to resort to computational methods to calculate such properties. In this work, we used molecular dynamics simulations in conjunction with metadynamics to calculate the free energy of dimerization of small aromatic rings comparing three models from popular online servers for atomistic force elds, namely G54a7, CHARMM36 and OPLS. We show that, regardless of the force eld, the proles for the dimerization free energy of these compounds are very similar. However, signicant care needs to be taken when studying larger molecules, since the deviations from the trends increase with the size of the molecule, resulting in force eld dependent preferred stacking modes, e.g. pyrene and tetracene. Our results provide a useful background for using topology builders to model systems which rely on stacking of aromatic moieties, relevant in areas ranging from drug design to supramolecular assembly.