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
non-polarizable 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.