Tetramethylammonium (TMA, N(Me) ) is a common cationic motif in biomolecular systems, notably present as choline in the polar headgroups of phosphatidylcholine lipids. Moreover, the TMA motif is important for choline-binding proteins and is integral to DNA expression regulation through the methylation of lysine residues in histones. Interestingly, in aqueous environments, TMA does not predominantly associate with anionic species but rather with hydrophobic aromatic molecules like benzene. This suggests that within proteins, TMA likely interacts with aromatic side chains of tryptophan, tyrosine, or phenylalanine, often forming complex structures such as aromatic cages. These configurations highlight TMAs significant role in cation-π interactions. Researchers have extensively studied the fundamental nature of cation-π interactions, demonstrating that they are primarily electrostatic, driven by the interaction between the aromatic systems quadrupole moment and the cation. Additionally, polarization forces are important, as the cation induces a dipole in the π-electron cloud. Significant efforts have been made to capture the cation-π interactions in standard non-polarizable force field molecular dynamics (FFMD) simulations. While often qualitatively describing the interaction geometry, these methods fail to achieve quantitative accuracy. Interaction energies are typically underestimated compared to quantum mechanical calculations, making FFMD simulations hardly suitable for tasks like identifying drug candidates reliant on cation-π binding. Khan et al. aimed at addressing this issue by optimizing the 12-6 Lennard-Jones (LJ) potential parameters in the CHARMM36 additive force field. Similarly, Turupcu et al. emphasized the significance of induction effects by introducing a 1/r 4 term, resulting in the 12-6-4 LJ formulation within the OPLS-AA force field. Felder et al. proposed that non-polarizable force fields can effectively describe cation-π interactions via suitable adjustments to the distribution of partial charges. How-ever, modifying the LJ potential and partial charges is challenging, as determining optimal parameters and justifying changes to the charges on both the cation and the aromatic molecule often lack a clear physical basis. Finally, explicit polarization methods, like Drude polarizable force fields, may enhance the accuracy of modeling of these interactions, but their higher computational cost can render them impractical for large systems such as proteins, membranes, or nucleic acids.