Charge scaling, also denoted as the electronic continuum correction, has proven to be an efficient method for effectively including electronic polarization in force field molecular dynamics simulations without additional computational costs. However, scaling charges in existing force fields, fitted at least in part to experimental data, lead to inconsistencies, such as overscaling. We have, therefore, recently developed a four-site water model consistent with charge scaling, i.e., possessing the correct low-frequency dielectric constant of 45. Here, we build on top of this water model to develop charge-scaled models of biologically relevant Li+, Na+, K+, Ca2+, and Mg2+ cations as well as Cl-, Br-, and I- anions, employing machine learning to streamline and speed up the parametrization process. On the one hand, we show that the present model outperforms the best existing charge scaled model of aqueous ions. On the other hand, the present work points to a future need for consistently and simultaneously improving the water and ion models within the electronic continuum correction framework.

• Publication type
• Journal Article MeSH

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