Latest improvements for CLC Drug Discovery Workbench

Improvements

• All NCBI server communication is now encrypted (uses HTTPS).
• Updated the URL to use for links to UniProt databases.
• Updated BLAST executables to be compatible with macOS Sierra. This change only affects Mac users.

Bug fixes

• Fixed a rare issue where some annotations could, but did not necessarily, go missing on sequences with greater than 1000 annotations of a given type on that sequence before the deletion and where the right-click context menu option “Delete selection” was used.

New features and improvements

• New Protein Optimizer allowing manual mutation and repair of amino acids, flipping of side chains, manual selection of side chain rotamers, and adaption of protein structure to point mutation.
• Ligand Optimizer now allows for modifications and creation of ring structures.
• 3D molecule viewer improvements:
  • Molecular surfaces can now be transparent
  • A clipping plane can cut into surfaces and secondary structure
  • Options for creating atom groups and visualizing hydrogen bonds have been improved

• Calculate Molecule Properties now has a new descriptor for calculating the number of flexible bonds in a ligand
• Metadata Management. Keep track of input files and import meta information for your samples.

Bug fixes

• Previously, an ester oxygen has been assigned the “hydrogen acceptor” atom type for docking scoring. Now it is instead assigned the “nonpolar” atom type, which is in line with the description of the PLANTS_PLP scoring function used in the workbench.
• Now properties for atom selections are displayed in the Property Viewer, also when the Ligand Optimizer is open
• A work around has been introduced for a java issue that occasionally resulted in the Workbench displaying an uninformative error requiring a workbench restart
• When doing manual mutations of protein residues in the 3D view, the new modeled side chain is now again aware of other atoms in the same chain
• Cofactors and ligands with incorrect substructure types in the Mol2 file are no longer imported as protein residues.
• Fixed an issue where one could not zoom in after zooming out fully on very large workflows.ing out fully on very large workflows.
• Fixed an issue that prevented a root folder on Windows drives from being used as a File Location.
• Fixed an issue where updating an existing installation on Windows would result in the .vmoptions file being deleted, which makes the Workbench run with the default Java configuration.

Bug fixes

• When doing manual mutations of protein residues in the 3D view, the new modeled side chain is now again aware of other atoms in the same chain.
• Added a work around to a java issue that occasionally resulted in the Workbench displaying an uninformative error and requiring a restart to continue working.
• Fixed an issue with running BLAST searches at the NCBI where an NCBI-generated error about their CPU usage limit being exceeded was not being reported transparently and a result of “no hits” was being reported instead.
• A fix was applied to avoid an exception in circumstances when the cleanup of downloaded files from BLAST failed.
• Fixed wrong display of “Supported format” when exporting elements from either the Folder Editor or the Local Search Editor.
• Fix of potential wrong file being saved when editing a file found via the Local Search Editor.
• Fixed an issue where the “Empty Recycle Bin” option was sometimes incorrectly unavailable.
• A fix was applied to avoid an exception in circumstances when the cleanup of downloaded files failed.

New features and improvements

• Biomolecule Generator. A new tool making it possible to generate or extract biomolecules based on symmetry information in PDB files.
• Replace atoms in ring systems in Ligand Optimizer. There is now support for replacing atoms in ring systems and optimizing the ring geometry.
• Manual rotation around bonds in Ligand Optimizer. A new option (‘rotate around bonds’) makes it possible to manually adjust the torsional rotations in a ligand.
• PDB header information. The PDB header is now available in the ‘Show History’ tab for Molecule Projects.
• Structure alignment improvements. When aligning structures from multiple Molecule Projects, an initial visualization is prepared where all molecules coming from the same Molecule Project will be visualized in the same color. Also, a combined sequence alignment can now be generated which is linked to the 3D view.
• BLAST. BLAST has been upgraded to BLAST+ 2.2.30 that includes a number of improvements and bug fixes. A full list of BLAST+ 2.2.30 changes can be viewed at http://www.ncbi.nlm.nih.gov/books/NBK131777.
• BLAST. The results of BLAST searches now include a new view, the Blast Hit Table.
• Better support for large structures. It is now possible to work with biological molecules with several hundred chains.
• General. Increased performance for gzip export.

Bug fixes

• BLAST. Fixed an issue with running blast searches at the NCBI where an NCBI-generated error about their CPU usage limit being exceeded was not being reported transparently and a result of “no hits” was being reported instead.
• PDB importer. When importing non-standard PDB files without version information, issues were raised for missing element types, even though element types should not be expected.
• PDB importer. When merging ligands with intermolecular bonds, intermolecular bonds to other molecules (such as proteins or cofactors) could be lost.
• PDB importer. Carbamoyl groups were not protonated correctly.
• Molecule file importers. Dialogs would incorrectly accept multiple files for input, even though only the first was imported.
• Ligand optimizer. Changing R/S stereochemistry for atoms in rings with a lone pair position was not possible.
• PDB exporter. If small molecules and protein chains share the same chain ID, this relation is preserved, also if the chain ID is renamed due to name clashes during export.
• 3D viewer. For Molecule Projects with a saved Binding Site Setup and with hydrogen bonds visualized, an exception would be shown when modifying the protonation of an amino acid in the binding site.
• 3D viewer. In rare cases, rendering would fail for Nucleic Acids containing nucleotides of unknown type with no nitrogens.
• General. On OS X, a left-click quickly followed by right-click was interpreted as double-click in some places of the user interface.

New features and improvements

• Homology Modeling. A new tool makes it possible to go from amino acid sequence to structure in two steps. The Find and Model Structure tool will identify suitable protein templates from the PDB and automatically build a structure model for a given input sequence.
• Constraints in Ligand Optimizer. It is now possible to keep parts of a ligand fixed while modifying it in the Ligand Optimizer. This can be used to work with covalently bound ligands, or to keep well established interactions in place during optimization.
• PDB exporter. It is now possible to export the molecule structures in a Molecule Project to a PDB file.
• Single point mutations in the 3D view. It is now possible to mutate or repair an amino acid from the context menu on an atom in the amino acid.
• Align to Existing Sequence makes it possible to connect a 3D protein chain to a sequence, sequence list, or an existing alignment
• Transfer Annotations makes it possible to create atom groups from sequence annotations (and vice versa) for connected sequences.
• Molecule importers:
  • New option to select a subset of molecules to import from SMILES or 2D.
  • Filter option added to molecule importers: Option to only import molecules with no issues attached.
  • Metadata (SDF data items) is now included when importing 2D molecules from SDF files. The metadata appears in the property viewer and in molecule tables.
  • When importing PDB files, the resulting Molecule Project now contains citation information (PDB ID and primary reference), which can be found in the ‘Show History’ view.
• • Improved PDB import of water molecules, DNA/RNA, and saccharides.
• Improved layout of the property viewer.
• Ligand optimized molecules now store energy terms as molecule properties.
• New column (‘Name of Molecule Project’) added to Docking Results.
• Workflows:
  • When installing a workflow in the workflow manager, the newly installed workflow is automatically selected.
  • The “Run” button in the workflow editor does not require a saved workflow anymore to be enabled.
  • In the execution wizard of a workflow the “Reset to default” button is now active.
  • All icons in the workflow editor are now on the left side.
  • Introduction of snippets: Parts of workflows can now be saved as a snippet and reused in other workflows.
  • Installed workflows: It is now possible to create a copy of an installed workflow and open the copy in the view area by clicking once and then right-clicking on the installed workflow in the toolbox. This brings up the option “Open Copy of Workflow”.
• Increased decimals for numbers when exporting table to CSV, tab delimited text, and Excel.
• Improved reporting of errors related to low disk space.
• Batching: Processes tab and analysis execution logs now display batch names in addition to analysis names for enhanced clarity.
• The External Application Client Plugin is now available directly from the Workbench Plugin Manager.

Bug fixes

• Search for PDB Structures at NCBI has been fixed to correctly show PDB deposit date and organism type.
• Fixed problem with links and text in tables that were being cut off when succeeding a link.
• Workflows:
  • In the workflow editor the “Reset to default” now always reverts to the right names.
  • In the workflow editor the validation is now correctly triggered when changing the configuration of an input element.
  • The workflow editor can now open workflows in which the graphical view of the workflow is corrupt.
  • Fixed an exception which could occur during workflow migration.
  • Data with the same name can now be bundled multiple times in a workflow installer.
  • Previously when a plugin contained custom actions and a workflow, the workflow could not be installed. This has been fixed.
  • Fixed problem with unlocked output names that previously could not be configured during execution of a workflow.
  • A workflow with configured data from a server is now automatically validated when connected to the server (when opened in the editor). Previously the workflow had to be closed and reopened first.
  • The original workflow file included in a workflow installer can now be exported directly without having to restart the workbench in advance.

• A problem with saved table settings that sometimes did not work has been fixed. The bug fix includes a more robust/generic way of saving table settings with different columns. To fix this problem, existing saved table settings should first be loaded on an object where it works (i.e. has the same columns as when it was saved); and then the table settings should be saved with the old name to overwrite the settings.

• Fixed an error that could cause batch processing to open all results rather than saving them.

• Metadata for phylogenetic trees: A bug has been fixed with import of metadata containing column names with colons.
• Fixed error when showing protein translations of annotations shorter than 3 bases.
• Two problems with the F1 help has been fixed; 1) When pressing F1 in a workflow tool wizard more than one help window appeared, and 2) Fixed problems showing help by pressing the F1 key in tool wizards.

New features and improvements

• Improved parsing of non-compliant PDB files.

Bug fixes

• Fixed a bug that did not allow docking results to be modified with the Ligand Optimizer.
• When running simultaneous docking simulations (e.g. in a workflow), in some cases the results could be corrupted.
• Fixed problem with scrolling to the relevant files when selecting objects as parameters in tool wizards.
• Fixed a problem that prevented BLAST operations when choosing to run these on the CLC Server.
• Pfam filtering bug fixed. Previously, Pfam only reported the first domain of each type in a query and as a consequence many domains were missed.

New features and improvements

• Ligand Optimizer – a tool to interactively modify, optimize, and understand ligand – protein binding.
• Protein Structure Alignment – high quality structural alignment of whole protein chains or selected regions of a protein.
• Calculate Molecular Properties – small molecule descriptors, including a XlogP implementation.
• Drug Discovery Server support – Molecule Docking and Virtual Screening now has improved support for multi-threaded and distributed execution across multiple machines (distributed execution requires a separate Drug Discovery Server license).
• Pfam domain search – using HMMER3 and supporting local download of the latest Pfam databases.
• 3D view state – all 3D visualization settings (including custom atom groups) can now be stored on a molecule project and shared with others.
• BLAST improvements – new tools for local execution and downloading, creation, and managing of BLAST databases.
• Project Tree improvements – new ways of showing hydrogen bonds and selecting nearby atoms. Improved visualization of intermolecular bonds. Atom groups are now stored on the Molecule Project and can be renamed. ‘Docking Target’ has been renamed to ‘Binding Site’. Labels on custom atom groups now show residue names if applicable.
• Molecule Preparation. Many improvements, including better handling of partial charges and more recognized chemical groups.
• The SDF importer will now import SDF metadata to Molecule Tables and Molecule Projects.
• New molecule color scheme where only the carbon atom color is varied.
• More sequence formats supported: Import of PIR (.pir) and SwissProt (.swp). Export in ClustalW, Fasta Alignment, and GCG Alignment formats.
• Import of Example Data and imports done through dragging files into the workbench and dropping them in the Navigation Area will no longer block the user interface while executing. Instead, the import happens as a background process that can be monitored and controlled via the Processes tab in the lower left corner.
• The CLC workbenches now support high resolution displays such as Apple retina displays.
• Advanced filtering on tables now includes the option to filter for a space, comma or semi-colon delimited lists of terms.
• Improved error messages due to low disk space.

Bug fixes

• Molecule Import. Better support for non-standard PDB files. Fixed a bug when importing 2D Mol2 files containing comments.
• Fixed some memory leaks where closed editors would stay in memory.
• Some external software (such as WebEX) could corrupt the visibility of molecules in the 3D view.
• Molecules in Molecule Tables could not be modified when the table was filtered.

Bug fixes

• Fixed problems causing an error when trying to uninstall plugins.
• Fixed issue with pausing and resuming running processes

New features and improvements

• The PDB importer has improved support for custom residues
• Fasta export now reports progress while executing

Bug fixes

• Fixed a bug that made PDB import fail on workstations with Turkish Locale settings
• Fixed problems where the workbench window would not position itself correctly on startup
• Fixed a bug that made access to data impossible because of a failed rename operation

New features

Initial release