Release Notes, Version 2026.1.1

The following products have new versions for this release. Other packages are unchanged from the previous release.

AI Fold Floes Release Notes

v0.2.6 April 2026

General Notice

  • This package is built using OpenEye-orionplatform==6.8.3, OpenEye-toolkits==2025.2.2, and OpenEye-Snowball==0.31.4.

Documentation Updates

  • Documentation has been added to guide the user on the Protein Sequence to AI Folded Structure Ligand Affinities Floe.

  • Documentation has been added to guide the user to create their own distributed MSA databases on Orion.

  • Documentation has been added to guide the user on different MSA databases that can be used with protein folding.

Floe Updates

  • Support has been added to supply template structures to Boltz to guide the folding process.

  • General error handling has been updated.

  • Minor typos have been fixed.

  • Input form examples are no longer quoted to avoid confusion with the actual input forms.

  • Output from the Protein Sequence to AI Folded Structure Ligand Affinities Floe now have unique names using a count incrementing method.

Cryptic Pocket Detection Floes Release Notes

v0.3.3 April 2026

General Notice

  • This package is built using OpenEye-toolkits==2025.1.1, OpenEye-orionplatform==6.8.3, OpenEye-Snowball==0.31.3, and OpenEye-orionmdcore==2.6.1.

Minor Changes

Generative Design Hit-to-Lead Release Notes

v2.8.1 April 2026

General Notice

  • This release is built using OpenEye-toolkits==2025.2.2, OpenEye-orionplatform==6.8.3, and OpenEye-Snowball==0.31.4.

  • OpenEye Generative Design Hit-to-Lead Floes v2.8.1 is released as part of the 2026.1 release.

Floe Updates

Large Scale Floes Release Notes

4.4.2 April 2026

General Notice

  • This package is built using “OpenEye-toolkits==2025.2.2” and “OpenEye-orionplatform==6.8.3”.

Features

  • The FastROCS Plus and Batch FastROCS Floes now support custom color force fields. Users can now select from supported OEColorFF types (ImplicitMillsDeanNoRings, ExplicitMillsDean, and ExplicitMillsDeanNoRings) or provide a user-defined color force field file.

  • The Batch FastROCS Floe now supports shape queries that include shape grids. The FastROCS Plus Floe does not support queries without molecules or queries containing shape grids and will fail if such inputs are provided.

  • The Batch FastROCS Floe now performs both shape and color optimization while performing overlay optimization of molecules. Previously, overlay used shape-only optimization while scoring and ranking used both shape and color. A shape-only optimization option is still available, but the default behavior now applies to both shape and color optimization.

Minor Changes

  • The Batch FastROCS Floe previously exposed six similarity types, including Shape Tanimoto, Shape Ref Tversky, and Shape Fit Tversky, that were not supported by the FastROCS Cube. The options are now limited to fully supported similarity types.

  • Default values for the Gigadock Warp Floe have been updated to better align with hardware requirements. The Fraction Train parameter and required disk space now better support the latest Enamine collection (~24.5B compounds). The floe also performs early validation with clearer guidance on parameter adjustments, and previously suggested disk requirements have been corrected.

  • The description of the Fraction Train parameter in the Gigadock Warp Floe has been updated to provide clearer guidance on the minimum required input collection size needed to run this floe based on the chosen fraction of the training compounds.

  • The package name has been changed from OpenEye-large-scale-floes to OpenEye Large Scale Floes.

  • The maximum hit list size in the Gigadock Warp Floe has been increased to 500,000 from 100,000.

  • The Batch FastROCS Floe previously included a FastROCS Shape column in hit list results, representing only the shape component of the score, while the corresponding color score was not shown. This column has been removed to improve clarity and consistency with subsequent ROCS rescoring.

  • Spot instance policy for GPU Omega instances in the Prepare Giga Collections Floe has been changed from Required to Preferred.

Molecular Dynamics Affinity Release Notes

v6.5.8 April 2026

General Notice

  • A Rapid FE-NES (Free Energy Nonequilibrium Switching) toggle switch has been added to the Equilibration and Nonequilibrium Switching Floe. When set to On (default: Off), jobs will run shorter MD simulations (1.5 ns) and fewer alchemical switches (20) to boost speed by 2x and throughput by 3x. Typical accuracy degradation is small (~0.2 kcal/mol).

  • Direct experimental affinity ingestion is now available (e.g., as originally provided in input .sdf files).

  • Experimental affinities may now be provided in concentration and log units (e.g., as \(IC_{50}\) and \(pIC_{50}\)).

  • The efficiency of MD simulations has been enhanced by optimizing cycling parameters in production simulations. Most MD-based Floes should now complete more quickly and incur reduced cloud compute costs (>10% improvement for standard MD).

  • Memory allocations for several cubes have been increased to better accommodate large-scale MD and NES simulations.

  • Primary input parameters have been moved to top sections of job forms in many Floes.

  • The package has been updated to run on Python 3.12 in order to align the software with modern runtime environments.

  • The package now pins oemdtoolbox 2.13.5, which includes bug fixes and compatibility with OpenMM ≥ 8. It also pins orionmdcore 2.6.1, which includes core dependency updates.

Floe Updates

  • Several minor updates have been made in the Edge Mapper for RBFE calculations Floe: Empty string hub inputs are now properly considered as unspecified; the Floe checks whether the selected map_type supports hubs and fails if a hub is specified for non-hub types; Edge scores are now shown as ‘N/A’ instead of 1.0 in the Floe reports when edge scoring is intentionally skipped; mitigated rare conditions in which OELOMAP graphs had many more than 1.5 edges per ligand.

  • Several minor updates have been made in the Nonequilibrium Switching Floe: The default maximum edge limit has increased from 100 to 500, and NES jobs now fail with a clear Floe Failure Report when the edge count exceeds this limit. To help prevent accidental all-to-all edge maps, NES Floes also abort when the input edge map is a complete graph with more than 100 edges. To intentionally run on a fully connected graph above this threshold, set the new force_complete_graph parameter (default: False) to True.

  • All Floe outputs now have default names.

  • Output dataset names and descriptions have been standardized for greater consistency. In particular, the Nonequilibrium Switching Floe now defaults to the output dataset name binding_affinity_output_dataset (was affinity_output_dataset).

  • Direct ingestion of experimental affinity from datasets selected for jobs is enabled in Equilibration and Nonequilibrium Switching, Nonequilibrium Switching, NES Result Utilities, Nonequilibrium Switching Recovery and Compare Experimental Affinity with End Point Analysis Results Floes. In addition, experimental affinities (and associated uncertainties) can also be provided in concentration and log units, e.g. in \(IC_{50}\) and \(pIC_{50}\), respectively.

  • Primary input parameters (required and optional) are placed in the top of the job form of Equilibration and Nonequilibrium Switching, Nonequilibrium Switching, NES Result Utilities, Nonequilibrium Switching Recovery and Compare Experimental Affinity with End Point Analysis Results Floes.

  • The default trajectory saving interval for MD Floes has been increased to 0.025 ns. For denser sampling, set the interval to 0.004 ns. For extended simulations, a larger interval is recommended to avoid excessive trajectory sizes and increased AWS storage cost.

  • The ‘MD API Dataset Converter’ Floe has been removed. This Floe is no longer needed because all MD Floes can automatically convert old datasets.

Molecular Dynamics Core Package

v2.6.1 April 2026

General Notice

  • This package is built using openeye-orionplatform >=5.1.1, <7, openeye-snowball >=0.26.0, openeye-toolkits >=2024.1.1, openff-toolkit >=0.17.0, <0.18, and parmed >=4.3.0, <5.

Updates

  • Support has been added for Python 3.10+.

  • The package has been updated to use ParmEd 4.3.0.

  • Compatibility has been added for NumPy 2 (<=2.2.6 due to constraints from ParmEd).

  • Compatibility has been added for the latest versions of MDTraj.

  • Support has been added for OpenMM up to 8.2 (was 8.1).

  • AmberTools have been validated and upgraded to version 24.8. This update also raises GAFF2 from version 2.11 to 2.2.20. Although this change is not explicitly noted in the AmberTools changelog, the Amber developers recommend using the latest GAFF2 release over the earlier version (see this email exchange for details). Set ligand_forcefield on ForceFieldCube to "Gaff_2.2.20" if you wish to use GAFF2. The original "Gaff_2.11" option is obsolete.

Cube Updates

  • A new option called orient_solute has been added to the Solvation Cube to control whether the solute should be oriented such that its principal axes align with the coordinate axes. In combination with the rectangular box shape, this option can be used to minimize box sizes and therefore reduce the simulation cost.

  • If you wish to use GAFF2, set ligand_forcefield on the Force Field Cube to "Gaff_2.2.20". The original "Gaff_2.11" option is obsolete.

ROCS X Floes Release Notes

v1.0.0 April 2026

General Notice

  • This package is built using OpenEye-toolkits==2025.2.1, OpenEye-orionplatform==6.8.2, and OpenEye-Snowball==0.31.3.

  • This is the first release of the OpenEye ROCS X Floes package.

Snowball Release Notes

v0.31.4 April 2026

General Notice

  • This package is built using OpenEye-orionplatform=6.7.0, OpenEye-toolkits==2025.2.1, OpenEye-szmap==1.7.1.1, and OpenEye-szybki==2.8.0.1.

Cube Updates

Structural Biology Floes Release Notes

v0.2.0 April 2026

General Notice

  • This package is built using OpenEye-toolkits==2025.2.1, OpenEye-orionplatform==6.8.3, OpenEye-Snowball==0.31.3, and OpenEye-orionmdcore==2.6.1.

Minor Changes

  • The Process X-ray Crystal Structures and Densities Floe has been added to enable WEMD simulation using densities computed from the X-ray crystallographic data as the target density map.

  • An issue has been fixed which terminated a simulation due to superposition errors from large conformational changes (RMSDs greater than 10 Å).

  • Chain alignment for homo-oligomeric proteins has been changed to 1:1 chain mapping.

Utility Floes Release Notes

v2.1.7 April 2026

General Notice

  • This package is built using OpenEye-orionplatform==6.8.0, OpenEye-toolkits==2025.2.1, and OpenEye-Snowball==0.31.4.

Floe Updates

  • The Design Unit to PDB File Floe has been renamed to be the DU to mmCIF/PDB File Floe, as the floe now has the option to export to either mmCIF or PDB file formats. It now defaults to mmCIF as the PDB format has been deprecated.

Recent Release History