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.

../_images/Make_receptor_3TPP.png

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.

View of the entire structures Zoomed in view on the 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.

../_images/DUReceptorSupport.png

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)

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

OEBio TK 3.1.1

New 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

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

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

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

MolProp TK 2.5.6

July 2021

Minor bug fixes

OEFF TK 2.3.1

July 2021

Minor internal improvements have been made.

Omega TK 4.1.1

July 2021

New features

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

More detailed changes are as follows:

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