A new pocket detection protocol successfully identified transient pockets on the protein surfaces of BCL-XL, IL-2, and MDM2. Because the native inhibitor binding pocket was absent or only partly detectable in the unbound proteins, these crystal structures were used as starting points for 10 ns long molecular dynamics simulations. Trajectory snapshots were scanned for cavities on the protein surface using the program PASS. The detected cavities were clustered to determine several distinct transient pockets. They all opened within 2.5 ps, and most of them appeared multiple times. All three systems gave similar results overall. At the native binding site, pockets of similar size compared with a known inhibitor bound could be observed for all three systems. AutoDock could successfully place inhibitor molecules into these transient pockets with less than 2 A rms deviation from their crystal structures, suggesting this protocol as a viable tool to identify transient ligand binding pockets on protein surfaces.