Frequently asked questions

How should the starting structure be selected for running the cryptic pocket detection floes?

Selection of the starting structure for running the cryptic pocket detection floe depends on the objective of running the floe. If the user is running the floe for validation purpose, the starting structure should be an apo structure of the protein of interest. If the user is running the cryptic pocket detection floe on their target protein, choose the state of the protein that best depicts the target state. For example, for finding a cryptic pocket that targets its oligomeric state, the user must ensure that the starting structure is in the correct oligomeric state. Similarly, correct substrate bound state should be chosen as the starting structure if the cryptic pocket needs to be identified in a specific substrate bound state. For example, for finding cryptic pockets in KRas in its inactive state requires the presence of GDP at its nucleotide-binding site.

Automated cryptic pocket detection floe fails due to a memory error. How to troubleshoot the job failure?

For large systems, the automated cryptic pocket detection floe is likely to fail with one of the following errors:

Failure in the “Preprocess Residue-probe Pairwise Distance Vectors for Clustering” cube

If this happens, run the Probe Occupancy Analysis floe by increasing the memory requirement of the Preprocess Residue-probe Pairwise Distance Vectors for Clustering cube under the Cube Parameters section. Use the Protein Sampling Data collection generated by the Automated Cryptic Pocket Detection with Probe Occupancy Analysis floe to run this floe.

Click on the System tab under Preprocess Residue-probe Pairwise Distance Vectors for Clustering to change the value of Memory (MiB) parameter. The default value is 65536 MiB. The memory requirement for your system depends on the system size and total number of iterations being analyzed.

Alternatively, you can choose to reduce the number of iterations being analyzed by changing the value of Start Iteration parameter under Selection Range For Trajectories.

Failure in the “Cryptic Pockets Reporter” cube

If this happens, run the Probe Occupancy Analysis floe by increasing the memory requirement of the Cryptic Pockets Reporter cube under the Cube Parameters section. Use the Protein Sampling Data collection generated by the Automated Cryptic Pocket Detection with Probe Occupancy Analysis floe to run this floe.

Click on the System tab under Cryptic Pockets Reporter to change the value of Memory (MiB) parameter. The default value is 65536 MiB. The memory requirement for your system depends on the system size, total number of pockets identified and number of cluster centers generated during the clustering step.

Additionally, you can choose to increase the value of Minimum Receptor Volume (default: 200) parameter under Pocket Design Unit Creator (Parallel). Increasing this value to a higher number will filter out conformations and pockets with smaller pocket volumes.