Release Notes, Version 2025.1

The packages below have been updated for this release. The other packages are the same as shipped with release 2024.2.2.

3D QSAR Models Release Notes

v1.1.5 February 2025

General Notice

This package depends on OpenEye-Orionplatform==6.2.0, OpenEye-Toolkits==2024.2.0, and OpenEye-Snowball==0.29.1.

Floe Updates

3D QSAR Model: Builder

A baseline 2D-GPR model is built by default and added to the output model dataset. The training set size for the 2D model is not necessarily the same as for 3D models because some molecules could be ignored in 3D model building for reasons such as failure of conformer generation, charge assignment, and so on.

3D QSAR Model: Predictor

Prediction for the COMBO model has been updated to be the weighted average of all individual models including 2D, with their corresponding prediction confidence as weights.

3D QSAR Model: Validation

Prediction for the COMBO model has been updated to be the weighted average of all individual models including 2D, with their corresponding prediction confidence as weights.

Histograms of pairwise similarities between validation and training sets have been added to the Floe Report.

3D QSAR Model: Interpretation

A new functionality has been added to optionally generate ROCS queries for virtual screening purposes.

Surface colors in the output dataset have been changed to be more consistent with atom colors in Orion.

New Floes

3D QSAR Model: Affinity Data Type Converter

The 3D QSAR Model: Affinity Data Type Converter Floe is a supplementary tool for converting affinity data from range or integer type to float type for model building.

ChemInfo Hit ID Release Notes

v2.0.1 February 2025

General Notice

This is a new package as a part of the Orion Floes reorganization. It includes Floes previously found in the Cheminfo Floes package.

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

Classic Lead Optimization Release Notes

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.

Format Conversion (ETL) Floes Release Notes

v6.3.1 September 2024

A bug has been addressed in which SMILES data in an input file following CXSMILES data caused a parsing error.
A bug has been addressed when exporting datasets to CSV files. All columns, or a subset thereof, can now be exported in cases when previously only Molecule and Molecule.Titled would have been exported.

Generative Design Floes Release Notes

v2.4.3 February 2025

Updates to the OpenEye Generative Design Hit to Lead Floes

All packages have been built using OpenEye-orionplatform==6.3.1, OpenEye-toolkits==2024.2.0, and OpenEye-Snowball==0.29.1.
In the Generative Structure Floe - Site selection, a bug has been fixed that required a parameter to be provided in the Reagent Molecule or Reagent Molecule fields. This is no longer required.

Updates to the OpenEye Generative Design Lead Opt Floes

All packages have been built using OpenEye-orionplatform==6.3.1, OpenEye-toolkits==2024.2.0, and OpenEye-Snowball==0.29.1.
In the Reaction & Reagent Database - Launch Product Enumerations Floe, the Output File Format parameter has been updated for a non-empty Output File Resource Name to reflect the only file type currently supported (.smi).
A bug has been fixed in the Reaction & Reagent Database indexing floes for reaction definition parsing that erroneously required functional group definitions, which should be optional.
The sulfon_amide reaction SMIRKS has been updated because it was disallowing the generation of aryl products. The update is in the OrgData reaction definition file, 2025_1_sample_reaction_classification.txt resource.

Large-Scale Floes Release Notes

4.2.3 February 2025

Fixes

An issue has been fixed that could cause the Gigadock Warp Floe to fail if a receptor with many constraints caused the vast majority of molecules to fail to dock because they cannot satisfy the constraints.

Changes

The Pareto Frontier Consensus Floe has been removed from this package. It has been added to the new Large Scale Floes Hit-to-Lead package.
The Multi Query 2D Similarity Floe has been removed from this package. It has been added to the new Large Scale Floes Hit-to-Lead package.

Large-Scale Floes Hit-to-Lead Release Notes

4.2.0 February 2025

Changes

This is the first release of the Large Scale Floes Hit-to-Lead package. This new package inherits the Pareto Frontier Consensus and Pareto Frontier Consensus Floes from the Large Scale Floes package. Included are documentation items involving those two floes, such as the Pareto Frontier Explanation.

Machine Learning Model Building Floes Release Notes

v0.12.1 February 2025

This package is built using OpenEye-orionplatform==6.2.0, OpenEye-toolkits==2024.2.0, OpenEye-Snowball==0.28.1, and OpenEye-floereport==6.2.0.

Feature Updates

There is now a baseline XGBoost model with every ML Build floe. The performance of these XGBoost models is reported in the Floe Report and output success model.
Several bug fixes have been made.

New Floe in this package

ML Predict: XGBoost for Small Molecules Floe

The XGBoost models built by default using ML Build floes can be used as input here. This floe can be used to predict the properties of small molecules using XGBoost from the ML Build floes. It will act as a classifier if the base model is a classifier trained on String and will act as a regressor if trained on Float. The floe autoselects the type of prediction based on the provided model. If the model was trained on a custom feature vector, please provide a field in the input molecule dataset containing the feature vector; otherwise, the floe will fail.

Molecular Dynamics Affinity Release Notes

v 6.5.3 February 2025

General Notice

We now support the interactive floe report for the Edge Mapper for RBFE calculations Floe, which allows a user to modify the perturbation map and save the changes as a dataset on Orion.
A new clustering-based edge map type, a multi-star map, has been added to the Edge Mapper for RBFE calculations Floe, and the star map hub selection scheme has been updated to select the representative parent molecule as a hub.
This version pins orionmdcore==2.5.1.
We now print clear error messages in the Floe Failure Report when a rectangular solvation box is chosen without any restraints (along with a Checker Bypass switch of the Bound Protein Ligand MD Health Checker Cube turned OFF). The floe is stopped with a Failed status when that happens. A distance threshold can also be provided to terminate MD runs of ligands if the ligands move beyond that threshold within the binding site after equilibration. This can be done via the shell_cutoff parameter of the Bound Protein Ligand MD Health Checker Cube. The names of those ligands that experience such egress will be noted in the Floe Failure Report. This feature is available in Equilibration and Nonequilibrium Switching, Plain Molecular Dynamics Floe, Ligand Bound and Unbound Equilibration for NES, Bound Protein-Ligand MD, Short Trajectory MD with Analysis, and Solvate and Run MD Floes.
We allow only one protein molecule as input (not to be confused with multiple chains) to the Short Trajectory MD with Analysis, Ligand Bound and Unbound Equilibration for NES, Equilibration and Nonequilibrium Switching, Solvate and Run MD, Bound Protein-Ligand MD, and Induced-Fit Posing (Confined) Floes. The floes fail quickly when that is found not to be the case.

Floe Updates

The Short Trajectory MD with Analysis and Analyze Protein-Ligand MD Floes now write the ligand binding interaction occupancy CSV file to the analysis result archive file.
The Edge Mapper for RBFE calculations Floe by default sets the number of CPUs to run the OEMapper Cube to 48, in order to speed up the perturbation map generation for the large ligand sets.
The Short Trajectory MD with Analysis Floe carries FreeForm evaluations only when using the FreeForm conformers as unbound sampling starting conformers. By default, the input bioactive conformation is used as a starting conformer for the unbound sampling.
In the Equilibration and Nonequilibrium Switching Floe, independent choices can be made for the solvation box shapes of the bound and unbound states of ligands. Whereas choosing a rectangular box for the bound state without imposing restraints (unless the Checker Bypass is ON) is still prohibited, box shape choice for the unbound state is not restricted by such restraints. This replicates what has been available in the Short Trajectory MD with Analysis Floe.
Users can now tune the frequency at which lines reporting the progress of MD production, equilibration, and warm-up stages are printed. They each have a default value (in ns). These defaults are larger than the previously fixed values. The change produces smaller log files that are easier to browse. This affects the Equilibration and Nonequilibrium Switching, Plain Molecular Dynamics Floe, Ligand Bound and Unbound Equilibration for NES, Bound Protein-Ligand MD, Short Trajectory MD with Analysis, and Solvate and Run MD Floes.
Promoted parameters of the Equilibration and Nonequilibrium Switching, Nonequilibrium Switching Recovery, Compare Experimental Affinity with Nes Results, Nonequilibrium Switching, and Ligand Bound and Unbound Equilibration for NES Floes have been placed in appropriate parameter groups that can be seen in their respective job forms.
Structured water analysis in the Short Trajectory MD with Analysis and Analyze Protein-Ligand MD Floes is turned off by default (Process Water Off) in the Trajectory To OEMols Cube.

Cube Updates

The default setting of holonomic constraints in NES has been changed in the NESGMX Cube. This setting now defaults to Bonds2H (default was previously All-Bonds). Along with some other changes to MD settings in NES, this helps to make the MD more numerically stable in NES switches. Although All-Bonds remains a selectable option, it is not recommended because of numerical instabilities in switches involving large mass changes (e.g., hydrogen to bromine).
A fatal port has been added to the Bound Protein Ligand MD Health Checker Cube for proper exception handling related to box shape choices that are inconsistent with restraints on the solute. Records transmitted through the failure report have also been refined to indicate which ligand moved out of the binding pocket after equilibration.
A Skip the edge scoring option has been added to the OEMapper Cube to enable the fast star map generation when a user specifies the hub ligand(s) of the star map.

Molecular Dynamics Core Package Release Notes

v2.5.1 February 2025

General Notice

Various aspects of Orion MD Core have been refactored and improved significantly in this version. Please note that some changes are unfortunately API-breaking, which may affect existing implementations. These changes are explicitly marked as (API-breaking) in the release notes below.

Cube Updates

The Solvation Cube has been updated as follows:
- The default salt concentration has been increased to 150 mM from 50 mM.
- The box size for small molecule is now determined considering the largest small molecule conformation along Omega sampling.
- A new md_cutoff_distance cube parameter has been defined to ensure that the minimum image convention is always enforced along MD runs.
- Ions in solutions are now placed far from the solute.
- A new min_number_of_salt cube parameter has been defined to ensure that the selected minimum number of ions are always present in solution. This parameter has been introduced to ensure future charge corrections change ligand mutations along RBFE calculations.
(API-breaking) The Collection Setting Cube has been refactored to use a new parameter, collection_fields, to specify which collection will be set on the input record. Additionally, a new string parameter, operation, has been introduced to define the action to perform on the collection. Supported values for operation are "open", "close", and "create".

Major Improvements

Support has been added for storing the bond orders in trajectories generated by the MD cubes using OpenMM as the engine. Bond orders can be accessed in output trajectory files as follows:

import mdtraj
# NOTE: mdcore must be imported for bond orders to be recognized by mdtraj,
# even if mdcore is not explicitly used
import orionmdcore

# load the trajectory from the last stage
traj_file = md_record.get_state_trajectory()
traj = mdtraj.load(traj_file)

# check if bond orders are present
for bond in traj.top.bonds:
    assert bond.order is not None

MDDataRecord has been improved in the following ways:
- MDDataRecord now internally uses the link, as opposed to integer IDs, to reference MD data stored as Orion resources (e.g., shards and files). ID fields from old records are automatically upgraded to links once MDDataRecord is initialized.
- MDDataRecord.get_value and MDDataRecord.set_value now return/expect Orion resources instead of links when dealing with link-type fields. For example:
```
# generic record
link_dict = record.get_value(MDFields.mddata)  # returns a link dict referencing the shard
link = APISession.get_link(link_dict)
shard = link.get_shard()

record.set_value(MDFields.mddata, link)  # sets with a link referencing the shard

# MDDataRecord
md_record = MDDataRecord(record)
shard = md_record.get_value(MDFields.mddata)  # returns the shard
md_record.set_value(MDFields.mddata, shard)  # sets with the shard
```
- Related utility functions and tools, including mdocli, have been refactored to support links stored on MDDataRecord.
- A new function, get_stage, has been added to MDDataRecord that can be used to retrieve MD stages by either stage index or name.
- MDDataRecord.get_stages and other MD stage getters now return an MDDataRecord instead of a generic record.
- (API-breaking) The input parameter of MDDataRecord.get_stage_by_name, MDDataRecord.has_stage_name, and MDDataRecord.delete_stage_by_name has been renamed from stg_name to name for improved clarity and simplicity. Additionally, the parameter can now be provided as either a positional or keyword argument. For example:
```
stage = md_record.get_stage_by_name("production")  # stage name as positional argument
stage = md_record.get_stage_by_name(name="production")  # stage name as keyword argument
```
- (API-breaking) The input parameter of the several member functions of MDDataRecord related to getting and setting the MD stage data has been changed such that the user can provide either the name or the index of the stage. The name of the parameter has been changed from stg_name to stage_id to reflect this new capability. Additionally, the parameter can now be provided as either a positional or keyword argument. For example:
```
traj_file = md_record.get_stage_trajectory("production")  # stage name as positional argument
traj_file = md_record.get_stage_trajectory(stage_id="production")  # stage name as keyword argument
traj_file = md_record.get_stage_trajectory(-1)  # stage index as positional argument
traj_file = md_record.get_stage_trajectory(stage_id=-1)  # stage index as keyword argument
```
Atoms in all components except for ligand and other_ligands are now reordered in MDComponents to enforce and satisfy the requirements for GROMACS topology. This should allow systems that were previously failing in GROMACS to be successfully simulated.
A new property, designunit, has been added to MDComponents for converting and retrieving an OEDesignUnit object from MDComponents.

Minor Improvements

Package dependencies have been updated to include the latest versions.
The use_gpu_cpu option in the OpenMMSimulations class has been renamed to "use_gpu" and changed to take Boolean values.
A precision option has been added to the OpenMMSimulations class, allowing users to specify the numerical precision for simulations when using the GPU. Supported values for this option are "single", "double", "mixed", and "auto". If precision="auto", the simulation defaults to mixed precision when available; otherwise, it falls back to single precision. The default value is "mixed", which requires mixed precision (i.e., fails when mixed precision is unavailable).

Bug Fixes

A rounding error has been fixed when calculating the total number of steps in MD runs.
An issue has been fixed that can lead to memory leaks when deserializing MDComponents from a record.
A bug has been fixed in the Delete MD Recovery Cube that could cause a deadlock.
An issue has been fixed where no record is emitted from NVT/NPT cubes when the simulation runtime is zero.
Various smaller bugs have been fixed.

Protein Modeling Release Notes

v1.0.0 February 2025

General Notice

This is a new package as a part of the Orion Floes reorganization. It includes Floes previously found in the Biomodeler Floes package.

This package is built using OpenEye-orionplatform==6.3.1, OpenEye-toolkits==2024.2.1, and OpenEye-Snowball==0.29.1.
The SiteHopper Search Floe has improvements to the GPU prescreen to generate hits with higher accuracy. Options have been added to filter hits based on a sequence similarity cutoff and a patch score cutoff.

Small Molecule Modeling Release Notes

v2.0.1 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 OEDocking - Dock into an Active Site for Virtual Screening Floe has been improved to provide clash-free docked poses by default. A new parameter quality has been added to the floe regarding the quality of output desired. The default setting Refined refers to optimizing the generated docked poses if there were any existing clashes. The Classic option does not perform any post optimization for clashes. The STMD option produces multiple clash-free poses, as recommended for Short Trajectory Molecular Dynamics.
The SZYBKI - Small Molecule Minimization Floe has a new parameter, H-only Optimization, enabling optimization of only the hydrogen atoms in the molecule.
The SZYBKI - Single point MMPBSA Floe now contains a new parameter, Use input charges, enabling the floe to work with existing charges in the molecule and bypassing assignment of AM1BCCELF10 charges.
The Dataset Classification – Bemis-Murcko Floe includes a bug fix for auto-detecting field names, which previously caused the floe to hang.
The EON - Shape and Electrostatic Similarity Alignment Floe has been modified to use cubes from snowball. The following snowball cubes are used, replacing the local cubes:

Snowball Release Notes

v0.29.1 February 2025

General Notice

This package is built using the following dependencies:
- openeye-orionplatform>=6.2.0,<7.0.0.
- OpenEye-Toolkits>=2024.2.0.
- OpenEye-szmap>=1.7.1,<2.0.0.
- OpenEye-szybki>=2.8.0,<3.0.0.

New Cubes

New Check clashes (Individual) and Check clashes (Series) Cubes have been added that enable checking if there are clashes between a ligand and the target protein.
A new Check Optimized Pose Cube has been added that enables checking if a ligand pose has moved too far out due to optimization.
A new Dock Output Quality preference Cube has been added that enables selection of the quality desired in docking output.
New EON Overlay, EON Overlay (Multi Query), and Combine EON Queries Cubes have been added that enable electrostatic overlays using the new Eon toolkit.

Cube Updates

The following issues have been fixed in the Generate Chomp 2D Fragments Cube:
- Input molecules without a title are given a title of Molecule.
- The cube now properly uses the text contents from the file coming through the smarts_port.
The following features have been added to the Build 2D BROOD Database Cube:
- A new Report Only parameter produces a quick report of fragments without attempting to emit the database fragments.
- A new init port accepts existing database collections, fragments of which are ignored in the newly built library.
- A new info port emits information about fragments accumulated during library building.
Behavior of the following cubes related to CHOMP has been improved to track memory usage and process the maximum amount it can handle instead of failing due to lack of memory.
- Build 2D BROOD Database
- Generate BROOD Database
The Chomp Report Cube has been improved to provide more comprehensive information.
The Brood Hit list Cube now emits comprehensive information on hit list building through a summary port.
The Brood Report Cube now provides comprehensive information on hit list generation, along with the details of the clustering and the hit molecules.
The Sage force field in the following cubes now points to the latest supported Sage version (2.1.0) in the associated toolkit:
The constant for conversion from KT to kcal has been updated from 0.59 to 0.592 in both the MMPBSA (Series) and MMPBSA (Individual) Cubes.
The Freeform Conf Prepare Ensemble Cube now properly uses the bound conformer when an input ensemble of given molecules is passed through a field other than the primary molecule field.
The following cubes now accept molecules with up to 40 heavy atoms as query molecules:
The Spruce DU to Mol Cube now fails if it does not find the specified components.
The Loop Builder Cube now adds a conformer ID for each generated conformer.
The Spruce Minimize Design Unit Cube Cube now recalculates interactions after minimization.

Utility Floes Release Notes

v2.0.1 February 2025

General Notice

This is a new package as a part of the Orion Floes reorganization. It includes floes previously found in the Classic, Cheminfo, and Biomodeler Floes packages.

This package is built using OpenEye-orionplatform==6.3.1, OpenEye-toolkits==2024.2.1, and OpenEye-Snowball==0.29.1.

Floe Updates

The following improvements and modifications have been made to the SPRUCE - Protein Preparation Floe:
- Metadata handling has been improved. Metadata file input is promoted with improved descriptions and better logging if a metadata file was not matched to an input structure file.
- The Add Ligand Smiles parameter has been added to better identify global ligand metadata and tautomer states.
- The handling of receptors for covalently bonded ligands has been improved.
- MTZ data handling has been updated after recent changes to the RCSB offerings of the EDMAPS Announcement.
The Calculate Average Precision Floe has been removed.

Release Notes, Version 2025.1

3D QSAR Models Release Notes

v1.1.5 February 2025

General Notice

Floe Updates

New Floes

ChemInfo Hit ID Release Notes

v2.0.1 February 2025

General Notice

Classic Lead Optimization Release Notes

v0.15.1 February 2025

General Notice

Floe Updates

Format Conversion (ETL) Floes Release Notes

v6.3.1 September 2024

Generative Design Floes Release Notes

v2.4.3 February 2025

Updates to the OpenEye Generative Design Hit to Lead Floes

Updates to the OpenEye Generative Design Lead Opt Floes

Large-Scale Floes Release Notes

4.2.3 February 2025

Fixes

Changes

Large-Scale Floes Hit-to-Lead Release Notes

4.2.0 February 2025

Changes

Machine Learning Model Building Floes Release Notes

v0.12.1 February 2025

Feature Updates

New Floe in this package

Molecular Dynamics Affinity Release Notes

v 6.5.3 February 2025

General Notice

Floe Updates

Cube Updates

Molecular Dynamics Core Package Release Notes

v2.5.1 February 2025

General Notice

Cube Updates

Major Improvements

Minor Improvements

Bug Fixes

Protein Modeling Release Notes

v1.0.0 February 2025

General Notice

Small Molecule Modeling Release Notes

v2.0.1 February 2025

General Notice

Floe Updates

Snowball Release Notes

v0.29.1 February 2025

General Notice

New Cubes

Cube Updates

Utility Floes Release Notes

v2.0.1 February 2025

General Notice

Floe Updates

Recent Release History