Troubleshooting

CaverDock cannot compute the lower-bound trajectory

There are several possible reasons, which may prevent CaverDock from computing the lower-bound trajectory.

  • A part of the tunnel is too narrow and therefore it forms a strong repulsive barrier. This situation needs manual inspection: CaverDock saves only the part of the lower-bound trajectory, which was successfully computed. The missing part of the trajectory probably contains a strong repulsive barrier such as a residue preventing the ligand from moving through the tunnel. The receptor geometry needs to be fixed by adding flexibility to side-chain residues or using a different snapshot of the receptor.

  • The ligand is forced to move against the active site bottom. This problem arises from a geometrical analysis of the tunnel where the geometrical approximation of the tunnel is too deep. An easy solution is to use the --dock_like parameter to navigate CaverDock where to start with the tunnel analysis.

  • The ligand is too complex to be successfully docked. CaverDock can be re-executed with higher exhaustiveness or a higher number of parallel workers.

  • The computation fails due to the stochastic nature of CaverDock. In this case, starting CaverDock once again should solve the problem.

CaverDock cannot compute the upper-bound trajectory

When an upper-bound trajectory cannot be computed, the user should inspect the lower-bound trajectory first. When the lower-bound trajectory already contains a high energetic barrier, the tunnel or the receptor geometry needs to be modified (see section Improving lower-bound energy). If it is not possible to improve the lower-bound trajectory, the selected ligand is likely not able to pass through the tunnel.

When the lower-bound trajectory does not contain any significant barrier, and the upper-bound trajectory is still not computed, CaverDock may not able to analyze the trajectory because of a high ligand complexity, or there is a bottleneck not detected by the lower-bound trajectory. This type of bottleneck can be found by inspecting the lower-bound trajectory in the vicinity of the disc, where the computation of the upper-bound trajectory has failed (CaverDock reports a number of the last disc, for which the upper-bound trajectory was computed). The number of snapshots in the lower-bound trajectory is equal to the number of discs. There should be visible non-contiguities in the lower-bound trajectory, which overpass the bottleneck (e.g. ligand flip, as shown in Figure visualising the schema of trajectory computation). The bottleneck needs to be manually identified and fixed (e.g. by using flexible side-chain residues).