Molecular modelling of cation–π interactions

Abstract

Cation–π 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–π 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–π 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.

Keywords:

• molecular modelling
• cation–π interactions
• cation–aromatic interactions
• proteins

Acknowledgements

This work was supported by an FQRNT Établissement de nouveaux chercheurs grant, by an NSERC Discovery grant and by PROTEO and GEPROM scholarships to EAO.