Sulfonated polystyrene (sPS) forms the hydrophilic blocks of styrene-olefin-styrene triblock copolymer ion-exchange membranes that are promising candidate materials for fuel cells and protective clothing. Here, we present a theoretical study of sPS interactions with water and nerve agent simulant dimethylmethylphosphonate (DMMP). We apply restricted Hartree-Fock (RHF) optimization in conjunction with the conductor-like screening model (COSMO) to study solutions containing fragments of sPS and Nafion (PhSO3-NH4+, CF3SO3-NH4+, (CF3)2CFOCF2CF(CF3)OCF2CF2SO3-NH4+) in water-DMMP binary solutions. Despite a lack of notable differences in the geometries of optimized ion-DMMP clusters, COSMO modeling based on the results of RHF minimization shows that the interactions of DMMP with PhSO3-, CF3SO3- and Nafion sidechain differ substantially, which results in a qualitative in the dependence of activity coefficients on the molality of model electrolyte. Molecular dynamics simulations of sPS and Nafion olygomers solvated in water and DMMP revealed a notable difference between the geometries of the skeleton in different solvents. The skeletons of both Nafion and sPS in DMMP were less folded and generally stiffer than in water. This conclusion agrees with experimental observations of deplastification effect by DMMP on some polymers. Notable dependence of the skeleton stiffness on the counterion was also observed. With Al+++ counterion, the polymer showed preference to “folded” conformations, with neighboring benzene rings parallel and sulfogroups close to each other, while extended conformations (with PhSO3- groups forming an angle of about 120deg and protruded into the solvent). Strong anisotripic structuring of DMMP around the SO3- group was revealed by means of three-dimensional spatial distribution functions. The anisotropic structuring of DMMP was much stronger in sPS as compared to Nafion, likely because PhSO3- group lacks the flexibility of Nafion sidechain.