Molecular modelling of cation-π interactions

Cation-pi interactions have long been considered a challenge for molecular modelling and a shortcoming of most of the commonly used biomolecular force fields. In this article, we provide an overview of current research on molecular modelling of cation-pi interactions, with an emphasis on applications to proteins and on our recent polarisable models based on the classical Drude oscillator. We describe the main approaches used to model cation-pi interactions in solution and illustrate their relevance to a few case studies: the stability of the villin headpiece subdomain, the blockade of potassium channels by quaternary ammonium ions, and the permeation of ammonium across transporters of the Amt/MEP family.