Using molecular dynamics simulations in an explicit aqueous solvent we examine the
binding of fluoride vs. iodide to a spherical macromolecule with both hydrophobic and
positively charged patches. Rationalizing our observations we divide the ion association in-
teraction into two mechanisms: (1) poorly solvated iodide ions are attracted to hydrophobic
surface patches, while (2) the strongly solvated fluoride and to a minor extent also iodide
binds via cation-anion interactions. Quantitatively, the binding affinities vary significantly
with the accessibility of the charged groups as well as the surface potential, therefore, we
expect the ion-macromolecule association to be modulated by local surface characteristics
of the (bio-)macromolecule. The observed cation-anion pairing preference is in excellent
agreement with experimental data.