Validation of the Applicability of Force Fields to Reproduce Ab Initio Noncovalent Interactions Involving Aromatic Groups

Abstract

Abstract Noncovalent interactions containing aromatic groups are of important significance to both the structure and function of proteins. It is necessary that modern force fields, especially those designed for biological molecules, are capable of describing these interactions. In this paper, the applicability of the CHARMm force field to the aromatic–amide (side-chain), aromatic–amide (backbone), aromatic–aromatic, aromatic–amine, aromatic–alcohol, aromatic–sulfhydrate and aromatic–aliphatic interactions are evaluated. For the first two interactions, the current CHARMm force field produces their interaction energies in good agreement with BSSE-corrected MP2 interaction energies. For the other four interactions, we found that the current CHARMm force field cannot produce their interaction energies to a satisfactory level of agreement with BSSE-corrected MP2 interactions. To make the CHARMm force field qualified for these interactions and simultaneously avoid changing the already defined parameters in the force field, the Lennard–Jones parameters (well depth and minimum distance) of the specific atom pairs related to these interactions are reparameterized through an automatic least square fitting program. With the new sets of parameters, the CHARMm force field is able to produce the interaction energies of these interactions in good agreement with their BSSE-corrected MP2 interaction energies.