Figure 8.

The problem of identifying a molecule such as tadalafil through docking, when given only PDE5 structures bound to dissimilar ligands, is challenging. By using multiple protein structures and a generalized approach to ligand ring search, Surflex-Dock finds solutions (top right) that are ranked very high among random screening compounds. Further refinement through protein pocket adaptation and pose family clustering produces a high-confidence pose prediction (middle right) that clearly matches the correct bound configuration of tadalafil. Movements within the protein pocket as part of the docking process are typically not large (bottom right), but they can be crucial for correct pose ranking.