Release Notes

v0.11.2 December 2022

General Notice

• This package is built using OpenEye-orionplatform==4.5.4, OpenEye-toolkits==2022.2.2, and OpenEye-Snowball==0.25.3.

New Floes

Floe Updates

• The EON - Shape Alignment and Electrostatic Similarity Scoring floe now allows multiple molecules as query.

• The solvent model parameter in the following floes now has a new PB option.

  • SZYBKI - Ligand Minimization in a Rigid Active Site

  • SZYBKI - Ligand Minimization in a Flexible Active Site

• The target mask parameter in the GamePlan - Ligand Design with Water Analysis using SZMAP floe no longer include the solvent particles as part of the target protein by default.

• A new Floe Filter Docking Hits by Interactions has been added. This annotates docking results and receptor datasets with fields that can be used to filter the results based on the interactions between the docked/posed molecule and the receptor. The floe additionally calculates an interaction fingerprint, and reports the tanimoto score with the receptor bound ligand as the reference (if present). The floe works for both single and multi-receptor results from GigaDocking and the classic docking floes.

• The BROOD - 3D Fragment Replacement floe now fails sooner if a 2D input query is provided.

• The SZYBKI - Ligand Minimization in a Rigid Active Site floe now takes as its input:

  • A design unit containing the protein and the ligand to be optimized, or

  • A set of ligands to be optimized in a protein provided in a separate design unit

• The SZYBKI - Ligand Minimization in a Flexible Active Site floe is modified to provide separate output records for each conformer when a multi-conformer molecule is optimized

• The Calculate Atropisomerism floe now assigns ‘mmff’ partial charges to the molecule is no partial charges are present in the input.

• The OEDocking - Dock into an Active Site for Virtual Screening floe no longer fails when num poses option is set greater than 1.

v0.10.1 September 2022

General Notice

• This package is built using OpenEye-orionplatform==4.4.0, OpenEye-toolkits==2022.1.1, and OpenEye-Snowball==0.24.1.

Floe Updates

• The Receptor in Design Unit cube mishandled bioDUs. A new parameter and default was set for all SPRUCE floes that use this cube.

v0.10.0 July 2022

General Notice

• This package is built using OpenEye-orionplatform==4.4.0, OpenEye-toolkits==2022.1.1, and OpenEye-Snowball==0.24.0.

• All floes have a new brief parameter and floe categories.

New Floes

• A new SZYBKI - Single Point MMPBSA has been added that calculates single point MMPBSA scores for ligands in the context of active site.

• The CHOMP - Generate BROOD Fragment Database floe was added to generate a fragment database for the BROOD floe from a set of input molecules. The floe can be used to fragment molecules, filter the fragments, generate 3D conformations, organize and index the fragments for rapid searching, and write a Brood database.

• The Calculate Atropisomerism floe was added, which updates an existing dataset to include a boolean field indicating presence of atropisomerism and an image field containing a depiction of molecule torsion.

• The Calculate Dipole Moment floe was added, which updates a dataset with the dipole moment of molecules.

• The Assign Partial Charges floe was added, which calculates partial charges of molecules.

Floe Updates

• A new solvent model parameter has been added to the following floes. The error handling behavior of these floes have also been improved. These floes are also now robust against input molecules missing explicit hydrogen atoms.

  • SZYBKI - Ligand Minimization in a Rigid Active Site

  • SZYBKI - Ligand Minimization in a Flexible Active Site

• The EON - Shape Alignment and Electrostatic Similarity Scoring floe now keeps all the input dataset record fields in the generated output dataset records.

• The FreeForm - Bound Ligand Configurational Free Energies with SZYBKI floe now keeps all the input dataset record fields in the generated strains output dataset records, along with having those fields being kept in the generated ensembles dataset records.

• The GamePlan - Ligand Design with Water Analysis using SZMAP no longer fails if the input molecule was missing title.

• The POSIT - Ligand Guided Small Molecule Posing now reports an additional field containing the posit method that was used for a prediction. The floe also now properly passes records to failed dataset in cases when posit fails due to low probability or clash as desired.

• The maximum allowable value for hitlist from the

  ROCS - Shape Based Alignment for Virtual Screening

  has been increased to 1,000,000.

• The POSIT - Ligand Guided Small Molecule Posing floe was modified to produce Interaction Map, Contact Map, and Unpaired Map diagrams.

• The following changes were made to the OMEGA - Conformer Generation for Macrocycles floe

  • Do not expose random_seed_field as a promoted parameter

  • Do not hide the iter_cycle_size parameter

• The OMEGA - 3D Conformer Ensemble Generation Floe was modified to filter macrocycle molecules using the ParallelMacrocycleFilterCube prior to the stereo enumeration process.

• The SPRUCE Protein Preparation Floes were modified with a new path where a reference structure can be generated as part of the Floes, instead of being a separate run prior to prep of a larger dataset.

• The SPRUCE Protein Preparation Floes were modified such that the failure floe reports is providing more actionable error messages and improved detail logging per structure.

v0.9.0 December 2021

General Notice

• This package is built using OpenEye-orionplatform==4.2.5, OpenEye-toolkits==2021.2.0, and OpenEye-Snowball==0.23.0.

New Floes

• A new ROCS Query Model Builder has been added that builds OEShapeQuery from a set of input bound ligands.

Floe Updates

• The following modifications have been made to the ROCS - Shape Based Alignment for Virtual Screening floe.

  • Ability to work with custom color force fields

  • Floe output no longer suppress hydrogen in the generated hits

• The floes SPRUCE - Protein Preparation from PDB Codes Floe and SPRUCE - Protein Preparation from PDB Files Floe have been updated to enable pocket finding in the event that Spruce does not find a ligand during structure preparation. The pocket search is done using OEPocket, and the result will be a set of design units each focused on a detected pocket.

• A output hitlist dataset from the OEDocking - Dock into an Active Site for Virtual Screening floe no longer automatically contain the input receptor design unit in the first record. A flag has been added to optionally add that as a separate but first record in the output dataset.

• The POSIT - Ligand Guided Small Molecule Posing floe has been modified with the following:

  • Can now generate multiple poses, and provides an option to use either only the best receptor or all receptors in doing so

  • The Design Units in the output records now contain receptors

  • A pose (if generated) is set into the record, even if the record goes to the failure port due to clash or low probability

• The SZYBKI - Ligand Minimization in a Flexible Active Site floe can now be used to minimize a ligand dataset against a protein in a separate design unit, in addition to minimizing a ligand and a protein containing within the same design unit.

• The following floes are now able to accept custom SMIRNOFF force fields. The latest OpenFF forcefield sage_openff200 has also been added, and is the current default, with internally generated am1bcc_elf10 charges.

  • SZYBKI - Small Molecule Minimization

  • SZYBKI - Small Molecule Hydrogen-Only Minimization

  • FreeForm - Aqueous Ligand Configurational Free Energies with SZYBKI

  • FreeForm - Bound Ligand Configurational Free Energies with SZYBKI

• The following floes are now able to accept custom SMIRNOFF force fields for small molecule components of a protein-ligand complex optimization, where the protein interactions are defined with the ff14sb. A new ff14sb_parsley has also been added, and is the current default.

  • SZYBKI - Ligand Minimization in a Rigid Active Site

  • SZYBKI - Ligand Minimization in a Flexible Active Site

• Ionic state can now be choosen in the following FreeForm floes:

  • FreeForm - Aqueous Ligand Configurational Free Energies with SZYBKI

  • FreeForm - Bound Ligand Configurational Free Energies with SZYBKI

• The output records of the Bound Ligand Configurational Free Energies datasets from the FreeForm - Bound Ligand Configurational Free Energies with SZYBKI floe now contains following additional fields in the conformer records

  • Partner (ensemble) conformer index

  • Partner (ensemble) conformer relative energy

  • Partner (ensemble) conformer deltaG

• A bug preventing use of Short Trajectory Molecular Dynamics (STMD) Floes output to be used as input to the FreeForm floes have been fixed.

• A bug in output for the Fingerprint Search - Small Scale 2D Similarity floe has been fixed to properly generate failed outputs and a failure report.

• A bug in the Substructure Search - Small Scale Substructure Matching floe was fixed where selected parts of the input query molecule were not searched, and instead the entire query molecule was searched. Now the floe will only search for selected parts of the query input.

• The query image in the BROOD - 3D Fragment Replacement floe report is now properly generated irrespective of if the floe was ran with or without a protein input.

• FastROCS has been removed from the list of mode choices in the OMEGA - 3D Conformer Ensemble Generation floe, as the results were not usable as-is in a FastROCS floe.

v0.8.3 June 2021

General Notice

• This package is built using OpenEye-Snowball==0.21.0 and the associated OpenEye-orionplatform.

New Floes

• The Classic Szybki Ligand in Flexible Protein Floe was added, which is a tool for optimization of ligands in a flexible protein active site. Both the ligand and the flexible part of the protein are modified to perform the optimization.

• The Classic ReceptorInDU Floe was added, which creates receptors in input DUs.

• The Classic Spruce - Import Prepared PDB Files was added, which uses Spruce to generate an OEDesignUnit object used by downstream OpenEye modelling applications in Orion, such as docking, posit, gameplan, or short-trajectory MD.

Floe Updates

• The Classic OEDocking and Classic Posit floes were adjusted to work properly with both OEB and DU receptors.

• The Classic OEDocking floe was modified to put the DU on a new field for the first docking record.

• The Classic Posit, Classic Szybki Ligand in Fixed Protein, Classic Szybki Free Ligand, and Classic Szybki Ligand Hydrogen floes were updated to use the ParallelLigandChargeCube instead of the (deprecated) LigandPrepCube.

• Fixed bug so that Classic Spruce: ETL Floe now handles input of files with .gz extension correctly.

• Floe failure report names were changed to include the title of the floe.

• Improved floe descriptions and floe parameter descriptions.

• Standardized floe success and failure output behavior with the floe_endgame function from the snowball package.

v0.7.1 November 2020

General Notice

• This package is built using OpenEye-Snowball==0.20.0 and the associated OpenEye-orionplatform.

Floe Updates

• The Classic Substructure Search Floe no longer fails when there are no hits.

• The Classic Macrocycle Omega Floe will produce the same number of conformers when it runs multiple times on the same input molecule.

• The Classic OMEGA Floe no longer re-flips input molecules. It also no longer flips specified nitrogen stereo centers.

• Promoted Cube parameters for all Floes now appear in the order specified by the Floe author in the Orion Job Form.

• The IdeaGroup column in the Classic BROOD Floe results has been renamed to ClusterID.

• The Classic Gameplan Floe now promotes errors of Gameplan log file to the floe report.

• The Classic Spruce - Prep from PDB Codes Floe no longer expose “Add Interaction hints as a promoted parameter”

• The Classic Spruce - Prep from Files Floe no longer expose “Add Interaction hints as a promoted parameter”

v0.6.2 August 2020

General Notice

• Upgrades to use OpenEye-Snowball==0.19.3.

v0.6.1 August 2020

General Notice

• Upgrades to use OpenEye-Snowball==0.19.1 and the associated OpenEye-orionplatform

New Floes

• New Classic Shapequery To Record Floe reads shape query from a file and outputs it to a dataset.

• New Classic Spruce - OEDesignUnit Type Updater has been added to convert datasets containing design units in the old Blob type to the new Types.Chem.DesignUnit type, which is required if a user wants to visualize the design unit in the 3D viewer. The Floe retains the old Blob type for backwards compatibility for this release, and merely adds the new fields.

Floe Updates

• Classic Spruce - Prep from PDB Codes and Classic Spruce - Prep from Files Floes now by default include loop modeling for gaps in protein structures. Preparation times are expected to increase, dependent on the number and lengths of the missing loops.

• Classic Szybki Free Ligand Floe and Classic Szybki Activesite Ligand Floe no longer fail when the solvent model is set to PB.

• The Classic BROOD Floe has been improved to align depictions of hits with the non-changing part of the BROOD query.

• The Classic OMEGA Floe now supports ‘fix molecule’ and ‘fix smarts’ to fix an portion of the input molecule.

• Support of Open FF 1.0 has been added to the following Floes. PARSLEY_OPENFF100, PARSLEY_OPENFF111 and PARSLEY_OPENFF120 are added as predefined choices, and an .offxml file that defines a SMIRNOFF force field can also be used as input.

  • Classic Szybki Activesite Ligand

  • Classic Szybki Free Ligand

  • Classic Szybki Ligand Hydrogen

  • Classic FreeForm Conformer Energies

  • Classic FreeForm Restriction Energies

• The Classic ROCS Floe has been updated to suport a shape query as well as a query molecule.

• The Classic Szybki Activesite Ligand Floe now assigns charges to proteins if they are not charged. The Floe used to fail if the protein is not charged.

Removed Floes

• The Classic Spruce - OEDesignUnit Upload Floe has been removed, as Orion now automatically can ETL OEDU files to records.

v0.5.2 April 2020

General Notice

• Upgrades to use OpenEye-Snowball==0.18.2 and the associated OpenEye-orionplatform

New Floes

• The spruce Floes refactored into two new Floes, the old Floes have been removed. The refactor of the Floes has removed the need to run multiple Floes to prepare strutures for modeling, furthermore, the Floes now write a single dataset containing multiple design unit records. The Floe can take multiple files or PDB codes, e.g. it is possible to prepare all the structures for a given target in parallel providing a single optional reference to superpose all the structures to.

  • Classic Spruce - Prep from PDB Codes

  • Classic Spruce - Prep from Files

Floe Updates

• Classic Posit has been improved to not always require high-memory machines.

• Classic OEDocking now fails more cleanly on bad receptor input.

• Classic Substructure Search now generates an additional output of un-matched compounds.

v0.4.0 November 2019

General Notice

• Upgrades to use OpenEye-Snowball==0.17.2 and the associated OpenEye-orionplatform

• The Classic Floes BETA package no loger exists. All of the Floes from the BETA package are now merged to the main package.

New Floes

• New Floe Classic Macrocycle Omega has been added to generate conformers of macrocycle molecules

• New Floe Classic Szybki Ligand Hydrogen has been added to optimize ligand hydrogen atoms positions

• New Floe Classic FreeForm Restriction Energies has been added to estimate restriction energies on bound ligands based on Force field based Conformational FreeForm calculation.

• New Floe Classic EON has been added to rank database molecule against query based on Electrostatics similarity.

• New Floe Classic Substructure Search has been added to find molecules containing MDL query patterns of interest.

Floe Updates

• The following Floes have been improved for robustness and are moved from the BETA package to the release package.

  • Classic FreeForm Conformer Energies: Floe for conformer free energies

  • Classic FreeForm Solvation Energies: Floe for solvation free energies

  • Classic Szybki Free Ligand: Floe for free ligand optimization

  • Classic Szybki Activesite Ligand: Floe for active-site ligand optimization

  • Classic 2D Similarity: Floe for fingerprint based 2D similarity

  • Classic Gameplan: Floe to analyze ligands to generate modification hypothesis

  • Classic BROOD: Floe to generate new Leads

• The Classic Posit Floe modified to use the capabilities of the newly modified Posit toolkit.

• The Classic ROCS Floe is enhanced with ability to work with multi-conformer query.

• The Classic Omega Floe enhanced with an optional Maximum Number of Conformers parameter.

• The Classic ROCS and Classic OEDocking Floes have been enhanced with a switch to turn on/off depiction of images.

v0.3.6 September 2019

General Notice

• Upgrades to use OpenEye-orionplatform==1.1.4 and OpenEye-Snowball==0.16.6

• The Classic Floes package is deployed in two parts: (1) OpenEye classic Floes: contains Floes that are robust and well behaved; (2) OpenEye classic Floes BETA: contains Floes that are functional but may be ill-behaved to some inputs. Floes from the BETA package would be moved to the standard package, as they are improved over time.

New Floes

• A specialized Floe for generating single 3D structure from a 1D/2D molecule.

• A Floe has been added to convert OEDesignUnits prepared outside of Orion to the format of output datasets produced by Classic Spruce Prep.

• A set of Floes have been added to prepare Unprepped datasets required for input to Classic Spruce Prep.

Floe Updates

• The Classic OMEGA Floe is now simplified to generate conformers for predefined use case based modes.

• The Classic ROCS Floe now produces more focused result fields, and responds properly to the user choice of sorter type field to produce the hitlist.

• The following Floes have been improved to better respond to bad inputs, and provide a comprehensive report on total or partial failure of the underlying jobs: * Classic Omega * Classic ROCS * Classic Docking * Classic Posit

• The Classic SPRUCE Prep Floe has been simplified, with many input parameters removed in favor of a robust set of defaults. The primary input to the Classic Spruce Prep Floe is an Unprepped PDB/MTZ dataset. An Unprepped input dataset can be generated using one of the following following Floes also in Classic Spruce: * Classic Spruce: PDB Code * Classic Spruce: PDB Codes File * Classic Spruce: PDB File Each of these Floes produce Unprepped input datasets for Classic Spruce Prep, and require either an input PDB code, a text file of PDB codes, or an input PDB file respectively.

v0.3.3 July 2019

General Notice

• Upgrades to use OpenEye-orionplatform==1.0.0 and OpenEye-Snowball==0.16.0

v0.3.1 June 2019

General Notice

• Upgrades to use OpenEye-orionplatform==0.2.5 and OpenEye-Snowball==0.14.0

New Floes

• A specialized Floe for running Classic ROCS with a single reference.

• A specialized Floe for running Classic POSIT with a single receptor.

Floe Updates

• The Multi-receptor Classic POSIT Floe now promotes a parameter to specify the minimum required memory, and another parameter to specify the poser cash size. The Floe also throws exception if sufficient memory for the job is not requested.

• The Multi-receptor Classic ROCS Floe now promotes a parameter to specify the minimum required memory. The Floe also throws exception if sufficient memory for the job is not requested.

• The Classic OEDocking Floe now works properly even when the input ligand records contains ‘ConfField: Chemgauss4 Score’ field.

• The Classic OEDocking Floe no longer produce docked pose with unusually high docking scores.

• The Classic GamePlan Floe now produces a Floe report to show GamePlan results and app log files.

• The Classic BROOD Floe now produces a Floe report to show BROOD results and app log files.

• The Classic Gameplan Floe now takes either a ligand/protein pair or a DesignUnit as input.

v0.2.5 March 2019

General Notice

• Upgrades to use OpenEye-orionplatform==0.1.14 and OpenEye-Snowball==0.13.6

New Floes

• New Floe for prepping a protein structure using Spruce.

• Floes for running wrapped app versions of GamePlan and BROOD.

• A specialized Macrocycle conformer generation Floe with Omega.

Floe Updates

• The Classic OEDocking Floe and Classic POSIT Floe now promote a parameter to specify the field on the record in which the receptor can be found.

• The FreeForm Conf Floe was modified to use new Conformer Splitter and Merger Cubes in Snowball.

• Every Cube which uses a Expand Confs to Mols Cube now defaults to not exanding conformers.

v0.2.2 September 2018

General Notice

• Upgrades to use OpenEye-orionplatform==0.1.7 and OpenEye-Snowball==0.13.3

• Added Release Notes

Floe Updates

• The Classic OEDocking Floe and Classic ROCS Floe now default to not generating report images, although this functionality can be restored via a parameter on each Floe.