Cation-π interactions involving the tetramethylammonium motif are prevalent in biological systems, playing crucial roles in membrane protein function, DNA expression regulation, and protein folding. However, accurately modeling cation-π interactions where electronic polarization plays a critical role is computationally challenging, especially in large biomolecular systems. 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. This approach, while not specifically designed for cation-π interactions, is shown here to significantly improve predictions of the structure of an aqueous tetramethylammonium-pyridine complex as compared to neutron diffraction data. This result, together with computational predictions for the structure of the aqueous tetramethylammonium-phenol complex, underscores the potential of ECC as a versatile method to improve the description of cation-π interactions in biomolecular simulations.

• MeSH
• Cations chemistry   MeSH
• Quaternary Ammonium Compounds * chemistry   MeSH
• Neutron Diffraction MeSH
• Molecular Dynamics Simulation * MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Cations MeSH
• Quaternary Ammonium Compounds * MeSH
• tetramethylammonium MeSH Browser