Figure 2. Accurate de novo prediction of protein-bound water molecule positions.

(A) Recovery of experimentally-observed water molecules (blue) and true positive rates of predicted water molecules (red) are shown with SPaDES, Fold-X with explicit water molecule modeling, and HADDOCK refinement with a 2.0 Å distance cutoff critera between predicted and experimentally-resolved waters. Higher fractional rates, ranging from zero to one, indicate increased accuracy of the predictions. (B-E) Examples of predicted water positions are shown for two protein-protein complexes and two integral ligand-bound membrane proteins: (B) barnase in complex with barstar, (C) colicin E2 immunity protein in complex with colicin E9 DNase, (D) A_2a adenosine receptor bound to the ZM241385 ligand, and (E) bacteriorhodopsin bound to the retinal ligand. Blue spheres: water molecules observed in protein X-ray structures (“experimental waters”). Green spheres: de novo predicted water molecules (“predicted waters”). Ligands are shown in magenta sticks. See also Figure S2, Table S1.