(a) Radial distribution function (RDF) between the amantadine amino group and water oxygen atoms, extracted from a 200 ns simulation. The RDF g(r) function (blue, left axis) shows a strong peak near 2.7 Å, associated with waters forming hydrogen bonds to the ammonium group. The cumulative integrated intensity ∫ g(r) (red, right axis) indicates that 3.5−4 waters are associated with the ammonium on average. The second broad peak near 4.8 Å represents the bridging and Gly34 waters and integrates to approximately 5−6 waters, in good agreement with the crystallographic structure. (b) RDF between the spiro-adamantyl amine amino group and water oxygens, extracted from a 200 ns simulation. Four waters associated with the ammonium group are observed, in agreement with the crystal structure.The second peak near 8 Å reflects more distant waters between His37 and Trp41 of the channel.