Quantifying the Strength of a Salt Bridge by Neutron Scattering and Molecular Dynamics

The molecular structure and strength of a model salt bridge between a guanidinium cation (side chain group of arginine) and the acetate carboxylic group in an aqueous solution is characterized by a combination of neutron diffraction with isotopic substitution and molecular dynamics simulations. The present neutron scattering experiments provide direct information about ion pairing in the solution. At the same time, these measurements are used to assess the quality of the force field employed in the simulation. We show that a standard nonpolarizable force field overestimates the strength of salt bridges. In contrast, accounting for electronic polarization effects via charge scaling allows to quantitatively reproduce the experiment. Such simulations are used to quantify the weak character of a fully hydrated salt bridge. Finally, on top of the canonical hydrogen-bonding binding mode, we uncover another interaction motif involving an out-of-plane hydrophobic contact of the acetate methyl group with the guanidinium cation.