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CHANGELOG.md

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Changes

1.2.1

  • Fixed a bug in generating multiple non-aromatic ring conformations. This functionality worked correctly when Gypsum-DL was originally published (e.g., with rdkit 2020.03.1). But due to changes made to more recent versions of rdkit, Gypsum-DL produced only one ring conformation, even if multiple were reasonably possible. It now produces multiple ring conformations even on recent versions of rdkit (e.g., 2023.03.1). We recommend using the lastest version of rdkit.
  • Gypsum-DL now uses AllChem.ETKDGv3 if it's available.
  • Modernized codebase some. Python2 no longer officially supported.
  • Updated copyright year to 2023.

1.2.0

  • Added to the Durrant-lab filters to compensate for an amide-related bug in MolVS, one of Gypsum-DL's dependencies. MolVS sometimes tautomerizes NC(=O)C[*] to N\C(O)=C\[*], so the Durrant-lab filters now remove any tautomers with substructures that match the SMARTS string [$(N)]C(=C)[$([OH]),$([O-])].
  • Previously, the Durrant-lab filters only removed terminal iminols, which are improbable tautomers of terminal amides. According to DataWarrior, internal iminols (e.g., C\N=C(\C)O) are also improbable, so these are now removed as well.

1.1.9

  • Improved error handling when loading SDF files that are poorly formatted (e.g., that do not specify charged nitrogen atoms). Gypsum-DL depends on RDKit for SDF loading, and RDKit apparently cannot handle these errors. If you find that Gypsum-DL skips many of your compounds with a Warning: Could not convert some SDF-formatted files to SMILES... error, consider using an SMI (SMILES) file instead.

1.1.8

Updated README.md to help some users who were having trouble installing RDKit.

1.1.7

  • Updated the README.md file, specifically the Important Caveats section.
  • Modest speed improvements when enumerating compounds with many chiral centers. (No need to enumerate far more compounds than will ultimately be used, given the values of the thoroughness and max_variants_per_compound user parameters.) This update should also allow Gypsum-DL to more efficiently use available memory.
  • Similar speed and memory improvements when enumerating compounds with many double bonds that have unspecified stereochemistries.

1.1.6

  • Corrected minor bug that caused Durrant-lab filters to inappropriately retain some compounds when running in multiprocessing mode.
  • Fixed testing scripts, now that Durrant-lab filters remove iminols.

1.1.5

  • Updated Dimorphite-DL to 1.2.4. Now better handles compounds with polyphosphate chains (e.g., ATP).
  • Minor updates to the Durrant-lab filters:
    • When running Gypsum-DL without the --use_durrant_lab_filters parameter, Gypsum-DL now displays a warning. We strongly recommend using these filters, but we choose not to turn them on by default in order to maintain backwards compatibility.
    • Added filter to compensate for a phosphate-related bug in MolVS, one of Gypsum-DL's dependencies. MolVS sometimes tautomerizes [O]P(O)([O])=O to [O][PH](=O)([O])=O, so the Durrant-lab filters now remove any tautomers with substructures that match the SMARTS string O=[PH](=O)([#8])([#8]).
    • Added filters to compensate for frequently seen, unusual MolVS tautomerization of adenine. The Durrant-lab filters now remove tautomers with substructures that match [#7]=C1[#7]=C[#7]C=C1 and N=c1cc[#7]c[#7]1.
    • Added filter to remove terminal iminols. While amide-iminol tautomerization is valid, amides are far more common, and accounting for this tautomerization produces many improbable iminol compounds. The Durrant-lab filters now remove compounds with substructures that match [$([NX2H1]),$([NX3H2])]=C[$([OH]),$([O-])].
    • Added filter to remove molecules containing [Bi].
  • Gypsum-DL now outputs molecules with total charges between -4e and +4e. Before, the cutoff was -2e to 2e. We expanded the range to permit ATP and other similar molecules.

1.1.4

  • Updated Dimorphite-DL to 1.2.3.
  • Added sys.stdout.flush() commands to ParallelMPI.run (see gypsum_dl/gypsum_dl/Parallelizer.py) to ensure that print statements properly output in large MPI runs.

1.1.3

  • Gypsum-DL used to crash when provided with certain mal-formed SMILES strings. It now just skips those SMILES and warns the user that they are poorly formed. See Start.py:303 and MyMol.py:747.
  • Durrant-lab filters now remove molecules containing metal and boron atoms.
  • Some Durrant-lab filters are now applied immediately after desalting. We discovered that certain substructures cause Gypsum-DL to delay during the add-hydrogens step, specifically when Gypsum-DL generates the 3D structures required to rank conformers. Removing these compounds before adding hydrogens avoids the problem.
  • Improved code formatting.
  • Made minor spelling corrections to the output.

1.1.2

  • Bug fix: thoroughness parameter is now correctly recognized as an int when specified from the command line.

1.1.1

  • Updated Dimorphite-DL to version 1.2.2.
  • Corrected spelling in user-parameter names. Parameters that previously used "ennumerate" now use "enumerate".
  • Updated MolVS-generated tautomer filters. Previous versions of Gypsum-DL rejected tautomers that changed the number of specified chiral centers. By default, Gypsum now rejects tautomers that change the total number of chiral centers, both specified and unspecified. To override the new default behavior (i.e., to allow tautomers that change the total number of chiral centers), use --let_tautomers_change_chirality. See README.md for important information about how Gypsum-DL treats tautomers.
  • Added Durrant-lab filters. In looking over many Gypsum-DL-generated variants, we have identified several substructures that, though technically possible, strike us as improbable. See README.md for examples. To discard molecular variants with these substructures, use the --use_durrant_lab_filters flag.
  • Rather than RDKit's PDB flavor=4, now using flavor=32.
  • PDB files now contain 2 REMARK lines describing the input SMILES string and the final SMILES of the ligand.
  • Added comment to README.md re. the need to first use drug-like filters to remove large molecules before Gypsum-DL processing.
  • Added comment to README.md re. advanced approaches for eliminating problematic compounds.

1.1.0

  • Updated Dimorphite-DL dependency from version 1.0.0 to version 1.2.0. See $PATH/gypsum_dl/gypsum_dl/Steps/SMILES/dimorphite_dl/CHANGES.md for more information.

  • Updated MolVS dependency from version v0.1.0 to v0.1.1 2019 release. See $PATH/gypsum_dl/gypsum_dl/molvs/CHANGELOG.md for more information.

  • Gypsum-DL now requires mpi4py version 2.1.0 or higher. Older mpi4py versions can result in deadlock if a raise Exception is triggered while multiprocessing. Newer mpi4py versions (2.1.0 and higher) provide an alternative command line execution mechanism (the -m flag) that implements the runpy Python module. Gypsum-DL also requires -m mpi4py to run in mpi mode (e.g., mpirun -n $NTASKS python -m mpi4py run_gypsum_dl.py ...-settings...). If you experience deadlock, please contact us immediately.

    To test your version of mpi4py, open a python window and run the following commands:

    >>> import mpi4py
>>> print(mpi4py.__version__)
3.0.1
>>>

  • Updated the examples and documentation (-h) to reflect the above changes.

  • Added a Gypsum-DL citation to the print statement.

1.0.0

The original version described in:

Ropp PJ, Spiegel JO, Walker JL, Green H, Morales GA, Milliken KA, Ringe JJ, Durrant JD. Gypsum-DL: An Open-Source Program for Preparing Small-Molecule Libraries for Structure-Based Virtual Screening. J Cheminform. 11(1):34, 2019. [PMID: 31127411] [doi: 10.1186/s13321-019-0358-3]