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.

CNRS Université de Paris UPR 9080 Laboratoire de Biochimie Théorique 13 rue Pierre et Marie Curie 75005 Paris France

Institut de Biologie Physico Chimique Fondation Edmond de Rotschild PSL Research University Paris France

Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences Flemingovo nam 2 16610 Prague 6 Czech Republic

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