Cation-pi Interactions in Biomolecular Simulations by Neutron Scattering and Molecular Dynamics: Case Study of the Tetramethylammonium Cation
Abstract
Cation-$\pi$ interactions involving the tetramethylammonium motif are prevalent in biological systems, playing crucial roles in membrane protein function, DNA expression regulation, or protein folding. However, accurately modeling cation-$\pi$ interactions in molecular dynamics is computationally challenging, especially in large biomolecular systems where electronic polarization plays a critical role. This study implements a physically justified electronic continuum correction (ECC) to the CHARMM36 force field, scaling ionic charges by a factor of 0.75 to effectively account for electronic polarization without additional computational overhead. Here, this approach, while not specifically designed for cation-$\pi$ interactions, is shown to significantly improve predictions of the structure of an aqueous tetramethylammonium pyridine complex as compared to neutron diffraction data. These results underscore the potential of ECC as a versatile method to improve description of cation-$\pi$ interactions in biomolecular simulations.
