Modeling induction phenomena in amino acid cation– $$\pi $$ π interactions

Abstract

Cation– $$\pi $$ interactions are widely recognized as an important class of interactions, notably in biology and supramolecular chemistry, participating in molecular recognition and association phenomena. Numerical simulations relying on additive force fields perform usually poorly in modeling precisely these interactions. It is now well established that accurate reproduction of the interaction energy of a positively charged group bound to the $$\pi $$ -electron cloud of an aromatic ring requires an explicit treatment of induction effects by means of polarizable potentials. In this contribution, we compare critically the ability of the CHARMM Drude polarizable force field to describe a series of prototypical cation– $$\pi $$ interactions observed in proteins with that of the pairwise additive CHARMM36 force field. Toward this end, potentials of mean force characterizing the binding of amino acid side-chain models, namely ammonium and guanidinium cations, on the one hand, and toluene, para-cresol and 3-methylindole, on the other hand, have been determined within the extended adaptive biasing force framework.