OEApplications 2021.1

Release Highlights 2021.1

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 design units in a few minutes for proteins with similar binding sites to a query design unit. 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).

OEDocking: MakeReceptor (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 a design unit can now be created using the MakeReceptor GUI application, as well as the SPRUCE and ReceptorInDU command-line utilities.

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 automatically detects protein constraints, a functionality that was previously only available in MakeReceptor. The detected protein constraints are kept disabled by default, and can be completely turned off if desired. These constraints, along with any custom constraints, can be enabled or otherwise edited both via the OEMakeReceptor interface, or using commands from OEReceptorProteinConstraints 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 design unit 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 POSIT.

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

OS

Versions

Linux

RHEL7/8, Ubuntu18/20

Windows

Win10

macOS

10.14, 10.15, 11

General Notices

  • VIDA 5.0.0 is available as a separate download as part of this release.

  • New application SiteHopper has been added to the application bundle and can run on any NVIDA GPU-enabled Linux platform.

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

  • Ubuntu 16.04 is no longer supported

  • MacOS 10.13 is no longer supported.

Detailed Release Notes 2021.1

AFITT 2.5.3

July 2021

Minor Bug Fixes

  • Minor deprecation warnings have been removed.

Documentation Changes

  • Updated documentation to support newer WinCoot version (0.9.4.1 and beyond)

BROOD 3.1.5

July 2021

  • Minor internal improvements have been made.

EON 2.3.5

July 2021

Minor internal improvements have been made.

Zap TK 2.4.1

July 2021

Minor internal improvements have been made.

OEDOCKING 4.1.0

July 2021

New Features

  • The MakeReceptor GUI application has been extended to be a fully functional DesignUnit and receptor builder. A new design unit 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 in MakeReceptor.

Minor Bug Fixes

  • Apps will now fail with error message if an invalid database with no molecules is provided.

  • Spruce4Docking has been removed. We recommend using SPRUCE instead.

  • POSIT output now contains receptor filename as SD data.

  • ReceptorInDU now generates receptors and reports multiple design units in a single output OEDU file.

  • OEB2DUReceptor now converts and reports multiple design units within a single output OEDU file.

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.

OMEGA 4.1.1

July 2021

Minor Bug Fixes

  • Flipper now has an improved default output file name.

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.

MolProp TK 2.5.6

July 2021

Minor bug fixes

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

PICTO 4.5.2

July 2021

  • Minor internal improvements have been made.

OEDepict TK 2.4.6

July 2021

Minor internal improvements have been made.

pKa-Prospector 1.1.5

July 2021

  • Minor internal improvements have been made.

QUACPAC 2.1.2

July 2021

  • Minor internal improvements have been made.

Quacpac TK 2.1.2

July 2021

Minor internal improvements have been made.

ROCS 3.4.2

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.

SiteHopper 1.0.0

July 2021

This is first release of the SiteHopper application suite. SiteHopper can search a database containing hundreds of thousands of design units for proteins with similar binding sites to a query design unit in a few minutes using an NVIDIA GPU. SiteHopper can also create this database from a series of biomolecular structures in OEDU format. The SiteHopper application suite consists of the following applications:

  • sitehopper_build generates a database of patches from design units to be searched with sitehopper_search.

  • sitehopper_search searches a database of design units for proteins with binding sites similar to a query design unit.

  • A large database of patches based on the public is available for download in a platform-independent format.

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.

SPRUCE 1.3.0

July 2021

New Features

  • getstructure now retrieves structures using a secure HTTPS connection using openSSL.

  • A no-prep option has been added to SPRUCE to enable conversion of prepared structures into the OEDesignUnit format. This option supersedes all other options.

  • An optional -out parameter has been added to SPRUCE, for specifying the output filename. SPRUCE can write multiple design units per PDB file, and the default option is to write all of them to the single specified file. An additional option -warts has been added that will postfix a #n (n being an incrementing number) to the output filename.

  • An OEReceptor is now added by default when using SPRUCE. The feature can be turned off using the -add_receptors false flag. A -targetMask can be specified to augment the receptor content. Furthermore, these OEDesignUnits with receptors can be further edited in the make_receptor GUI application.

  • Options for setting the RMSD, sequence alignment score, and Tanimoto thresholds for validating the superposition result have been added to superposition.

  • The names of the available superposition methods for SPRUCE, enumsites, and superposition have been unified.

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 1.6.2

July 2021

  • Spruce4Szmap has been removed. We recommend using SPRUCE instead.

Szmap TK 1.6.2

July 2021

Minor internal improvements have been made.

SZYBKI 2.3.1

July 2021

New Features

  • A new option, parsley_openff1.3.1 has been added as a possible value for the -ff parameter in SZYBKI and in Freeform.

Minor Bug Fixes

  • The log file for SZYBKI has been updated with a note that option -exact_vdw might be used to improve convergence for ligand optimization inside a protein receptor when MMFF94 or MMFF94S force fields are used.

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.

VIDA 5.0.0

July 2021

New Features

  • VIDA has been updated and ships with the current toolkit release 2021.1.

  • VIDA has been updated to use Python 3.

  • VIDA has been updated to use Qt 5. In addition we have switched for PyQt to PySide2, providing full access to the Qt library via Python.

  • VIDA extensions have been updated to Python 3 and Qt 5.

  • VIDA now supports opening OEDesignUnits and recognized the OEDU file format. VIDA will also show OEReceptor information if stored on the OEDesignunit. OEDesignUnits will not be able to be saved in this release.

  • VIDA now supports opening MMCIF files.

  • File->Open Special->From PDB will now download an MMCIF file if a PDB file is not available for a particular PDB code.

  • Several toolbar icons have been updated

Major Bug Fixes

  • Improvements have been made regarding loading of state files

Removed features

  • Support for hardware stereo has been removed

  • The screenshot tool has been removed