Legacy Release Notes

v0.3.1 August 2025

General Notice

• This package is built using OpenEye-toolkits==2025.1.0, OpenEye-orionplatform==6.4.1, OpenEye-Snowball==0.30.0, and OpenEye-orionmdcore==2.5.4.

Minor Changes

• The Automated Cryptic Pocket Detection with Probe Occupancy Analysis, Combined Probe Binding Site Analysis, Probe Occupancy Analysis, Dynamic Probe Binding Analysis, and Exposon Analysis Floes will finish with the job status “Success” if no cryptic pockets are detected for a given target instead of a “Failed” completion. A Failure Report will be generated listing the potential reasons and next recommendations when no pockets are detected for a target.

• If users provide optional Important Residues input while running the Automated Cryptic Pocket Detection with Probe Occupancy Analysis, Combined Probe Binding Site Analysis, Probe Occupancy Analysis, Dynamic Probe Binding Analysis, and Exposon Analysis Floes, the center-of-mass distance between the user-defined Important Residues and Pocket Residues will be reported for each pocket in the Pocket Receptors output dataset generated by these floes.

Major Changes

• The Filter Trajectory Features Data Cube (previously named Preprocess Trajectory Analysis Data) has a seven-to-tenfold lower memory requirement. The Curate Cryptic Pockets Cube (previously named Cryptic Pockets Reporter Cube) has more than a twofold lower memory requirement. Collectively, these changes reduce the chances of failure due to memory error associated with cryptic pocket floe report generation while running the Automated Cryptic Pocket Detection with Probe Occupancy Analysis, Combined Probe Binding Site Analysis, Probe Occupancy Analysis, Dynamic Probe Binding Analysis, and Exposon Analysis Floes.

• The Dynamic Probe Binding Analysis is more than twelvefold faster in this version. The run cost for this floe is now expected to be fivefold less than the previous version.

• A new floe, Combined Probe Binding Site Analysis, that combines Probe Occupancy Analysis and Dynamic Probe Binding Analysis has been introduced. Running this floe eliminates the need to separately run the Probe Occupancy Analysis and Dynamic Probe Binding Analysis Floes for cryptic pocket detection.

• A new OEligandability-score based pocket ranking has been introduced. For each pocket reported by the Automated Cryptic Pocket Detection with Probe Occupancy Analysis, Combined Probe Binding Site Analysis, Probe Occupancy Analysis, Dynamic Probe Binding Analysis, and Exposon Analysis Floes, the total ligandabilty score; the ligandability score normalized by total surface points as well as by receptor volume; and the ligandability significance score will be reported in the Pocket Receptors output dataset.

v0.2.7 March 2025

General Notice

• This package is built using OEToolkits 2024.1.1, Orion Platform 6.1.2, and Snowball 0.28.0, Orion Molecular Dynamics (MD) Core 2.4.2.

Minor Changes

• The Cryptic Pockets Reporter Cube has a significantly lower memory requirement. This reduces the chances of failure due to memory error associated with cryptic pocket floe report generation while running the Automated Cryptic Pocket Detection with Probe Occupancy Analysis, Probe Occupancy Analysis, Dynamic Probe Binding Analysis, and Exposon Analysis Floes.

• Temporary checkpoint files and collection are deleted after the cryptic pocket analysis floes finish. This includes an auto-cleanup for the Automated Cryptic Pocket Detection with Probe Occupancy Analysis, Probe Occupancy Analysis, Dynamic Probe Binding Analysis, and Exposon Analysis Floes.

v0.2.5 September 2024

General Notice

• This package is built using OEToolkits 2024.1.1, Orion Platform 6.1.2, and Snowball 0.28.0, Orion Molecular Dynamics (MD) Core 2.4.2.

Minor Changes

• A fix has been made to allow analysis of protein structures with protonated histidine residue names (HIE, HID and HIP).

• An issue with display of pocket residues in the cryptic pocket analysis floe report has been fixed. It now displays the pocket residues when the protein chain IDs do not begin with “A” or when the protein chain IDs do not follow the alphabetical order.

v0.2.4 July 2024

General Notice

• This package is built using OEToolkits 2024.1.1, Orion Platform 6.1.2, and Snowball 0.28.0, Orion Molecular Dynamics (MD) Core 2.4.2.

Minor Changes

• A correction has been made in the axis of the 2D free energy projection on the normal modes.

• A default value for mutual information cut-off for pocket detection using the Dynamic Probe Binding Analysis and Exposon Analysis Floes is set to 0.00. This parameter is also now exposed to users under Cube Parameters.

• Faster receptor creation in the Probe Occupancy Analysis, Dynamic Probe Binding Analysis, and Exposon Analysis Floes makes them more time efficient.

• The documentation now includes an FAQ section.

v0.2.2 April 2024

General Notice

• This package is built using OEToolkits 2023.2.3, Orion Platform 6.1.2, and Snowball 0.27.1.

Note

There is a known incompatibility between datasets created by previous versions of Cryptic Pocket Detection and datasets used by this version. If you need assistance with this issue, please contact Support@eyesopen.com.

Major Changes

• The Automated Cryptic Pocket Detection with Probe Occupancy Analysis Floe is introduced for automated, end-to-end workflows for cryptic pocket detection with probe occupancy analysis using an input design unit prepared using Spruce.

• Three advanced Floes (Probe Occupancy Analysis, Dynamic Probe Binding Analysis, and Exposon Analysis) automate the cryptic pocket analysis process by integrating analysis of weighted ensemble protein sampling data, iterative clustering, cryptic pocket detection, and receptor creation.

• Weighted ensemble protein sampling data storage has been significantly refactored, which reduces the overall size by half and supports faster data find and read.

• Two new options have been added, Maximum Number of Selected Modes and Mode Filtering Property, in the Calculate Normal Modes Floe that allow for automatic rank and select modes based on specific mode properties. This feature is turned On by default in the Automated Cryptic Pocket Detection with Probe Occupancy Analysis Floe.

Minor Changes

• In addition to the Automated Cryptic Pocket Detection with Probe Occupancy Analysis Floe, individual sub-floes starting from the Solvate and Equilibrate Target Protein Floe to three cryptic pocket analysis Floes (Probe Occupancy Analysis, Dynamic Probe Binding Analysis, and Exposon Analysis) can be sequentially run for protein sampling and cryptic pocket analysis.

• Now the Run a Normal Mode-Guided Weighted Ensemble MD Simulation Floe generates and stores data in a V2 ShardCollection.

• The outputs have been changed from the Run a Normal Mode-Guided Weighted Ensemble MD Simulation Floe. Now the output dataset contains multiple records (one record per iteration) and only contains summary statistics for the simulation. All simulation data (e.g., weighted ensemble data, MD trajectories, simulation files) are stored in the output shard collection. The collection is now self-contained and required as input for downstream analysis Floes.

• The Subsystem Selection String option has been substituted with Environment Selection String in the Calculate Normal Modes Floe for ease of use. Now the system-environment framework is enabled by default in the Floe.

• The Continue a Normal Mode-Guided Weighted Ensemble MD Simulation Floe now takes the collection generated by the Run a Normal Mode-Guided Weighted Ensemble MD Simulation Floe as the input to resume the weighted ensemble protein sampling simulation.

v0.1.2 September 2023

General Notice

• This package is built using OEToolkits 2023.1.0, Orion Platform 5.1.1, and Snowball 0.26.0.

Minor Changes

• Fixes an issue related to “select string” parameter format in the Calculate Normal Modes floe.

• Enables support for non-canonical amino acids in the Solvate and Equilibrate Target Protein floe.

• A minor typographical correction in documentation for the Calculate Normal Modes floe.

v0.1.0 July 2023

General Notice

• This is the first release of OpenEye Cryptic Pocket Detection Floes.

• This package is built using OEToolkits 2023.1.0, Orion Platform 5.1.0, and Snowball 0.26.0.