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.