OEToolkits 2021.1

Release Highlights 2021.1

OEDocking TK: Receptors in Design Unit

OEReceptor as an integral part of an OEDesignUnit, with properly prepped structures and contained in an OEDU file, is fully integrated in all workflows. Receptors in an OEDesignUnit can now be created using the MakeReceptor GUI application, as well as the SPRUCE and ReceptorInDU command-line applications.

The MakeReceptor GUI application has been extended to be a fully functional DesignUnit builder in addition to building receptors. A new DesignUnit can be created from a PDB/MMCIF file (with or without an associated MTZ file), or by combining molecules from various molecule files of any format. SPRUCE options are exposed through a graphical interface giving users control over the level of preparation the structure should go through. Existing receptors, both in OEDU or OEB format, can also be opened and edited as desired, in MakeReceptor.

OEMakeReceptor now autmatically detects protein constraints. The detected protein constraints are kept disabled by default, and can be completely turned off if desired, functionality that was previously only available in the MakeReceptor application. Both the detected constraints and any custom constraints can be enabled and edited via the OEMakeReceptor interface, or using commands from OEReceptorProteinConstraint and OEReceptorCustomConstraints classes in the toolkit.

OEDocking receptor for the 3TPP BACE1 Complexed with Inhibitor with target structure, bound ligand, and a protein constraint. Displayed in MakeReceptor viewer.

Having the receptors as part of the OEDesignUnit with properly prepped structures makes it easier for the docked and posed structures to be used in further downstream modeling, which is especially necessary when working with protein force fields like FF14SB. The new receptors with properly prepped protein also enabled use of modern force fields like FF14SB and Parsley for structure optimization in flexible OEPosit.

OESiteHopper: Application Suite for Rapid Protein Binding Site Comparison

The 2021.1 release introduces SiteHopper, which can search a database containing hundreds of thousands of proteins in a few minutes for proteins with similar binding sites to a query protein. SiteHopper will output the most similar biomolecules, overlayed by binding site, for visualization and analysis. A visual representation of the binding site is also output. SiteHopper can also create databases for searching from a series of biomolecular structures in OEDU format.

SiteHopper finds proteins with similar binding sites which searching by sequence similarity would overlook. An example is shown in the figure below. 1UYG is a structure of human heat shock protein 90-alpha, bound to 8-(2,5-dimethoxy-benzyl)-2-fluoro-9H-purin-6-ylamine. 5IUN is a structure of the DesK-DesR complex, bound to AMP-PCP.

The image on the left shows the overlay of 1UYG (green) and 5UIN (light yellow), zoomed out to show the major structural differences between the two proteins. The image on the right zooms in on the binding sites, with a surface showing the type of residues present in each binding site. Blue represents acidic, red represents basic, yellow represents polar, and white represents non polar. Despite a sequence similarity of only 46%, 1UYG and 5IUN may be targetable by similar ligands, as they have very similar steric and electrostatic properties in their binding sites.

1UYG human hsp 90 (green) overlayed with 5UIN N-formyltransferase (yellow), full struture view (left) and binding site view (right).

VIDA 5: Major Update and OEDesignUnit Support

VIDA has undergone major changes including:

• Upgrade to Python3.

• Upgrade to Qt5 with PySide2 providing for user-interface improvements.

• Updated to run on the same platforms as OpenEye Toolkits and Applications.

This allows us to release VIDA along side the toolkits and applications in our twice-yearly releases.

In addition, VIDA now has support for MMCIF files and improvements to I/O from other file format types. VIDA can also read prepared protein structures in OEDesignUnit format produced with SPRUCE and MakeReceptor along with the receptor objects that are now stored on these design units.

VIDA DesignUnit Support with receptors showing the prepared beta-secretase structure 3TPP.

Supported Platforms

Package	Versions	Linux	Windows	macOS
Python	3.7, 3.8, 3.9	RHEL7/8, Ubuntu18/20	Win10	10.14, 10.15, 11
C++		RHEL7/8, Ubuntu18/20	Win10 (VS2017, VS2019)	10.14, 10.15, 11
Java	1.8, 11	RHEL7/8, Ubuntu18/20	Win10	10.14, 10.15, 11
C#			Win10 (VS2017, VS2019)

Related TK Versions

Toolkit	Version
OEChem TK	3.1.1
OEDepict TK	2.4.6
OEDocking TK	4.1.0
FastROCS TK	2.2.0
OEFF TK	2.3.1
Grapheme TK	1.4.3
Graphsim TK	2.5.2
Lexichem TK	2.7.3
OEMedChem TK	1.1.4
MolProp TK	2.5.6
Omega TK	4.1.0
Quacpac TK	2.1.2
Shape TK	3.4.2
Spicoli TK	1.5.2
Spruce TK	1.3.0
Szmap TK	1.6.2
Szybki TK	2.3.1
Zap TK	2.4.1

General Notices

• C++ CUDA-enabled toolkits and features are now supported on RHEL8 and Ubuntu20.

• Support for GCC 9.x has been added. Support for GCC 4.x and GCC 5.x has been dropped.

• Support for Python 3.6 has been dropped.

• Support for VS2015 has been dropped.

• Support for MacOS 11 has been added. Support for MacOS 10.13 has been dropped.

• OpenEye applications and toolkits have not been optimized for the M1 Mac but run under Rosetta 2.

Detailed Release Notes 2021.1

July 2021

New features

• OEZ has been made the default file format for storing molecules in OERecord objects.

• Two new functions, OECalcPMI and OEGetRadiusOfGyration, have been added. The first calculates the principal moment of inertia (PMI) for a molecule, and the second calculates the radius of gyration for that molecule using a previously calculated PMI.

• InChI has been updated to v1.06. A new option to OEInChIOptions supports generation of non-standard InChI strings with pseudoatoms present.

• Atom/bond SMARTS expressions can now be used as generic data for SMARTS queries.

• The function OEApplyStateFromRef now transfers stereo/chiral information from the reference state molecule.

Major bug fixes

• The function OEPerceiveResidues has been enhanced to properly recognize ACE (acetyl) and NME (N-methyl) capping groups, which used to cause unexpected behaviors. Recognition of the NHE and FOR capping groups has also been improved.

Minor bug fixes

• An issue that caused a crash in the OEPDBOrderAtoms function when running with preserveResOrder=True and molecules that do not have chain IDs has been fixed.

• An issue that caused OEApplyStateFromRef to return redundant matches when doing partial matching with long hydrocarbon chains has been fixed.

• An issue that caused OEDetermineConnectivity to break all bonds between atoms with wrong valences (possibly resulting in a broken backbone) has been fixed. It now tries to break the bonds between non-adjacent residues first and, if the valences of involved atoms are still wrong, all bonds.

Documentation changes

• Added documentation for the functions OEGetSoleNeighbor, OEGetSoleBond, OEGetSoleDoubleBond, and OEGetSoleSingleBond.

OEBio TK 3.1.1

New features

• Two new constructors have been added to the OEDesignUnit class. These constructors are intended to be used with prepared molecules. The two APIs are for liganded or apo-structures, where in the latter case site-residues indicating the binding site are required.

• Predicate versions of OEIsStandardProteinResidue and OEIsStandardNucleicAcidResidue have been added as OEIsStandardAminoAcid and OEIsStandardNucleicAcid, respectively.

• The OEReceptor class now stores a predicate that can be used to subset an OEDesignUnit class component. For example, a specific water molecule in the solvent component that should be used when generating the receptor grid and during docking.

• The function OESubsetDesignUnit and the method OEDesignUnit::GetComponents now take a predicate that will subset the component(s) they hit in the design unit.

• The functions OESubsetDesignUnit and OEUpdateDesignUnit will now clear the stored OEReceptor if the targetMask and targetPredicate of the receptor match the content being updated or subsetted away.

• Non-const methods for OEReceptor::GetCustomConstraints, OEReceptor::GetProteinConstraints, and OEReceptor::CustomConstraints::GetConstraintFeatures have been added giving access to edit constraint features.

Minor bug fixes

• Nitriles (C#N) are now recognized as hydrogen bond acceptors in interaction hint perception.

• Hydrogen bonds to moeities that are also interacting as saltbridges are now properly perceived.

• Amide NH atoms are now properly counted as as UnpairedLigandDonor when appropriate.

• The default for GetMaxCationPiAngle was reduced to from 50 to 40 degrees.

• The default for SetMaxNonIdealAcceptorAngle was increased from 70 to 90 degrees.

• The default for GetMaxNonIdealDonorAngle was increased from 50 to 70 degrees.

• Several intra molecular interaction types are now properly perceived with OEPerceiveInteractionHints

OESystem TK 3.1.1

Major bug fixes

• An issue that caused the string format method on the OEFieldType for double to be converted to int has been fixed. The format method now writes with a precision of 12.

• An issue that caused the string format method on the OEFieldType for double to add a .0 after a NaN has been fixed.

• An issue that caused the string format method on the OEFieldType for string and JSON to be elided if longer than 100 characters has been fixed.

• An issue with metadata flags not getting properly updated when a field with new metadata was set on an existing field has been fixed.

OEPlatform TK 3.1.1

New features

• ZSTD has been updated to version 1.4.9, resulting in improvements in compression and decompression performance for the OEZ file format.

OEGrid TK 3.1.1

Major bug fixes

• OEScalarGrid now preserves OEGridType through I/O.

OEMath TK 3.1.1

Minor internal improvements have been made.

OEDepict TK 2.4.6

July 2021

Minor internal improvements have been made.

OEDocking TK 4.1.0

July 2021

New features

• A predicate string can now be supplied to OEMakeReceptorOptions using OEMakeReceptorOptions::SetTargetPred. This povides a way to specify a select set of water molecules in an OEDesignUnit to be part of the receptor when the docking grid is constructed and used in subsequent docking calculations.

• OEMakeReceptor now auto-generates protein constraints. The constraints are left disabled by default for the docking calculations. These can be enabled using the toolkits, or the MakeReceptor GUI application. The auto-generation of the constraints can be turned off using the OEMakeReceptorOptions::SetAutoConstraints method in OEMakeReceptorOptions.

Minor bug fixes

• The default value for the OEMakeReceptorOptions::AddBox has been set to 0.0 in the OEMakeReceptorOptions class.

FastROCS TK 2.2.0

July 2021

New features

• A new method, OEShapeDatabaseScore::ExtractTransform, that extracts an entire transform (not just the post inertial frame transformation) has been added.

Minor bug fixes

• An issue with custom weights in FastROCS custom color has been fixed.

Grapheme TK 1.4.3

July 2021

New features

• Rendering of protein-ligand binding sites has been improved to handle new intramolecule types in the OEPerceiveInteractionHints function.

GraphSim TK 2.5.2

July 2021

Minor internal improvements have been made.

Lexichem TK 2.7.3

July 2021

New features

• Support for input of many common drug names has been added.

• Support for SMILES input of disubstituted alkenes when unknown subsituents are marked as * has been added. For example, SMILES input of *CCC* is now parsed and named as 1,3-disubstitutedpropylene.

Major bug fixes

• An issue with naming of highly branched carbons structures has been fixed.

OEMedChem TK 1.1.4

July 2021

Minor bug fixes

• OEMatchedPairOptions::ComboCuts has been added by default to all cut options.

MolProp TK 2.5.6

July 2021

Minor bug fixes

• An issue with OEGetRotatableBondCount counting carbamates and ureas as rotatable has been fixed.

OEFF TK 2.3.1

July 2021

Minor internal improvements have been made.

Omega TK 4.1.1

July 2021

New features

• Function OEOmegaSystemHasGPU has been added to test for availability of a GPU.

Major bug fixes

• A bug that caused a segmentation fault when zero was passed to the OEMacrocycleOmegaOptions::SetMaxConfs method has been fixed.

• And issue that prevented oeomega from using the GPU in child threads when OEOmegaIsGPUReady was called from the main thread has been fixed.

Minor bug fixes

• An issue with stereo specificity of the imino group (=NH) not being retained in a macrocycle has been fixed.

• An issue with loss of relative stereo marked atoms in macrocycle mode has been fixed.

Quacpac TK 2.1.2

July 2021

Minor internal improvements have been made.

Shape TK 3.4.2

July 2021

Major bug fixes

• A bug that caused some molecules to get a perfect Shape Tanimoto score of 1.0, even though their overlap was not optimal, has been fixed.

Spicoli TK 1.5.2

July 2021

Minor internal improvements have been made.

Spruce TK 1.3.0

July 2021

New features

• A molecule-based API for OEMakeDesignUnitFromPocket has been added.

• New high-level superposition APIs were added that unify the sequence-based (OEStructuralSuperposition) and shape-based (OESecondaryStructureSuperposition) APIs. This includes new classes:

  • OESuperpose that calculates different types of structural superposition.

  • OESuperposeOptions that allows users to control various behaviors of the superposition calculation (e.g. the superposition method).

  • OESuperposeResults which contains the transformation and scores of the superposition.

More detailed changes are as follows:

• The new OESuperpose class can take either OEMol or OEDesignUnit as the reference for the fit molecule(s). The reference molecule can be set by using the OESuperpose::SetupRef method, and the superposition can be calculated via OESuperpose::Superpose with the fit molecule supplied as one of its arguments.

• A new OESuperposeMethod namespace was added that contains the constants for different superposition methods. Functions OEGetSuperposeMethodName and OEGetSuperposeMethodFromName were added to obtain the superposition method’s name (as a string literal) from its designated constant and vice versa.

• Methods OESuperposeOptions::SetValidRMSD, OESuperposeOptions::SetValidSeqScore, and OESuperposeOptions::SetValidTanimoto have been added. These methods can be used to set score thresholds for validating superposition results in the new OESuperposeOptions class. The validity of the superposition result can be obtained by OESuperposeResults::IsValid from the new OESuperposeResults class.

• The new OESuperpose API returns an OESuperposeResults object that can be used to transform the fit molecule to its superposed position with its OESuperposeResults::Transform method. Alternatively, users can use OESuperposeResults::GetRotMatrix and OESuperposeResults::GetTranslation to obtain the rotation matrix and translation vector, respectively, for their analyses. The RMSD and sequence alignment score after the superposition can be obtained using OESuperposeResults’s OESuperposeResults::GetRMSD and OESuperposeResults::GetSeqScore methods for sequence-based superpositions, and the Tanimoto score can be obtained using OESuperposeResults::GetTanimoto.

  Please refer to the documentation for more information on these new superposition APIs.

Minor bug fixes

• A bug that caused the loop modeling algorithm to crash in rare instances has been fixed.

• Examples have been modified to use appropriate command-line arguments.

• An issue that caused style on OEProtonateDesignUnit has been fixed.

• An issue in OEMakeDesignUnitFromPocket that caused style to remain on both the previous binding site and the one defined from the pocket has been fixed.

• An issue with the return value of superposition when two structures cannot be superposed has been fixed. It now properly returns a -1.00 RMSD.

• A bug in superposition that resulted in a crash when using site residues that were not present on a design unit has been fixed.

• A bug that kept the insert code from its anchor residue when there was an N-terminal cap has been fixed.

Documentation changes

• Documentation has been added for the Iridium classification. Iridium.

Szmap TK 1.6.2

July 2021

Minor internal improvements have been made.

Szybki TK 2.3.1

July 2021

New features

• The latest version of the Open Force Field Initiative, Parsley 1.3.1, has been added to OEForceFieldType as built-in force field OEForceFieldType::PARSLEY_OPENFF131.

• Support for user-defined force fields has been added to OETorsionScan. Two new API points, OETorsionScanOptions::SetForceField and OETorsionScanOptions::GetForceField, have been added for setting and getting this value.

• Support for user defined dihedral angles has been added to OETorsionScan. Two new API points, OETorsionScanOptions::SetUserDefinedAngles and OETorsionScanOptions::SetUserDefinedAngles, have been added for setting and getting this value.

Zap TK 2.4.1

July 2021

Minor internal improvements have been made.

Previous Release History

• OEToolkits 2020.2.2
• Release Highlights 2020.2
• OEToolkits 2020.1.1
• OEToolkits 2020.1
• OEToolkits 2020.0
• OEToolkits 2019.Oct
• OEToolkits 2019.Apr
• OEToolkits 2018.Oct
• OEToolkits 2018.Feb
• OEToolkits 2017.Oct
• OEToolkits 2017.Jun
• OEToolkits 2017.Feb
• OEToolkits 2016.Oct
• OEToolkits 2016.Jun
• OEToolkits 2016.Feb
• OEToolkits 2015.Oct
• OEToolkits 2015.Jun
• OEToolkits 2015.Feb
• OEToolkits 2014.Oct
• OEToolkits 2014.Jun
• OEToolkits 2014.Feb
• OEToolkits 2013.Oct
• OEToolkits 2013.Jun
• OEToolkits 2013.Feb
• OEToolkits 2012.Oct
• OEToolkits 2012.Jun
• OEToolkits 2012.Feb
• OEToolkits 2011.Oct
• OEToolkits 2011.1
• OEToolkits 1.7.4
• OEToolkits 1.7.2
• OEToolkits 1.7.1
• OEToolkits 1.7.0