Classic Lead Optimization Release Notes

v1.0.4 August 2026

General Notice

• This package is built using OpenEye-orionplatform==6.9.0, OpenEye-toolkits==2026.1.0, and OpenEye-Snowball==0.32.4.

Floe Updates

• The BROOD - 3D Fragment Replacement Floe has gone through the following changes:

  • The Query Sketcher now offers three selection options that determine how the floe behaves, chosen directly within the sketcher.

    • Select atoms to keep: the default automatic query generation, where BROOD builds the query from the atoms that are not preserved.

    • Select atoms to replace: the classic selection, matching the floe’s legacy behavior.

    • Select atoms for linking/cyclization: the option to join two or three selected segments through a linking or cyclization search.

  • The floe can now run multiple queries in a single job, supplied either as several prepared BROOD queries or as multiple Query Sketcher instances, provided all queries derive from the same parent molecule.

  • The supported score types now depend on the selection option: Select atoms to keep supports the ROCS and ET score types, while Select atoms to replace and Select atoms for linking/cyclization support all three (ROCS, ET, and LinkOnly).

  • A Build Secondary option has been added and is enabled by default. When enabled, BROOD produces analogs in which several of the input molecule’s query regions are replaced simultaneously, in addition to the analogs where a single region is replaced.

  • Additional BROOD settings are now exposed as parameters, including Maximum Hits, Shape Cutoff, Ring Requirement, and strain-based filtering of the built analogs via Max Strain and Delta Strain.

  • The floe has been redesigned to better accommodate multiple queries and to expose more parallelization and optimization, improving throughput on large jobs. Database reading and the overlay stage are now more parallelized, allowing the floe to make more complete use of the available compute when processing large fragment databases.

  • The default memory requirements have been reduced across the final hit list and report, lowering the floe’s overall resource footprint.

  • The Floe Report has been rewritten with a redesigned, sectioned layout that presents the query depiction, cluster analysis, and per-query fragment hit details. A report is now always produced, and the optional report switch has been removed.

• The BROOD - Query Builder Floe has been updated to incorporate the automatic query creation and linking/cyclization modes described above.

• When an input molecule does not have any atropisomeric bonds, the Calculate Atropisomerism Floe no longer fails trying to depict atropisomers.

v0.16.3 December 2025

General Notice

• This package is built using OpenEye-orionplatform==6.4.1, OpenEye-toolkits==2025.2.0, and OpenEye-Snowball==0.31.0.

v0.16.2 August 2025

General Notice

• This package is built using OpenEye-orionplatform==6.4.1, OpenEye-toolkits==2025.1.1, and OpenEye-Snowball==0.30.1.

Floe Updates

• The default memory for the single-receptor Posit Cube has been increased to 4*1.8*1024 in the POSIT - Ligand Guided Small Molecule Posing Floe.

v0.15.1 February 2025

General Notice

• This package is built using OpenEye-orionplatform==6.2.0, OpenEye-toolkits==2024.2.0, and OpenEye-Snowball==0.29.1.

Floe Updates

• The CHOMP - Generate BROOD Fragment Database Floe has been improved as follows to improve usability and robustness:

  • A Report Only parameter has been added that would produce a quick report of fragments without attempting to generate the database.

  • The memory requirement per fragment has been reduced by keeping track of just a single source molecule instead of five.

  • Instead of failing due to lack of required memory, the floe now attempts to complete the task with the amount of fragments that it could process.

  • An Input Existing Brood Database parameter has been added to enable passing in an existing database, fragments from which should not be included in the newly created database.

  • The default setting has been adjusted for fragments larger than nine heavy atoms to be included in the database if the fragment is contained in at least two of the source molecules.

  • The zipped database, in .TAR.GZ format, is saved by default.

  • The floe no longer fails to write fragments when input molecules are missing titles.

• The BROOD - 3D Fragment Replacement Floe has gone through the following changes:

  • The Floe Report now provides comprehensive information on the hit list generation along with the details of the clustering and the hit molecules.

  • The default memory for the hit list generation cube has been increased to 48*1.8*1024

• The FreeForm - Bound Ligand Configurational Free Energies with SZYBKI Floe now properly uses the bound ligand from the primary molecule field when an input ensemble is provided by the user through a separate field.

• The BROOD - DB File to Collection Floe now generates a report if it fails to complete successfully for some reason.

• The BROOD - Query Builder Floe now generates a report if it fails to complete successfully for some reason.

• The POSIT - Ligand Guided Small Molecule Posing Floe now properly respects user choice for the Relaxation Mode parameter. The default for the Relaxation Mode has also been changed to Clashed, to ensure that generated poses are clash free by default.

• The Calculate Atropisomerism Floe now assigns AM1BCCELF10 charges by default and provides an option to change the default behavior.