A method for sampling macrocyclic conformational space (see
macrocyclemode below) has been added to OMEGA. This method uses a distance geometry approach to generate conformer ensembles for macrocyclic molecules. It can also be applied to linear and small ring-containing molecules but is substantially slower than OMEGA
OMEGA now includes five modes:
classic: the original customizable OMEGA interface
macrocycle: the conformer generator for macrocycles
rocs: the optimal conformer generator for ROCS
pose: the optimal conformer generator for pose prediction or docking
dense: the optimal conformer generator for FREEFORM
The classic mode is the original customizable OMEGA interface and the
macrocyclemode uses an adaptation of the distance geometry method of Spellmeyer et al. [Spellmeyer-1997]. All other modes use fixed optimal parameters of the original OMEGA interface for various downstream applications:
rocs: -maxconfs = 50 pose: -maxConfRange = "200,800", -rangeIncrement = 8 dense: -strictstereo = false, -ewindow = 15, -maxtime = 3600, -rms = 0.3, -maxrot = 20, -maxconfs = 20000
A new command,
oeomega, has been added to invoke these modes. In addition, the original
omega2command has been retained for backward compatibility. In all modes except
macrocycle, OMEGA automatically detects macrocycles and sends them to the fail file. The following are examples of
oeomegacommands to run these modes:
oeomega classic -in drugs.smi -out drugs_classic.oeb.gz oeomega macrocycle -in drugs.smi -out drugs_macrocycle.oeb.gz oeomega rocs -in drugs.smi -out drugs_rocs.oeb.gz oeomega pose -in drugs.smi -out drugs_pose.oeb.gz oeomega dense -in drugs.smi -out drugs_dense.oeb.gz
There are now two built-in torsion libraries in OMEGA in
classicmode: the original PDB-derived torsion library and a new CSD-derived library, “Guba,” based on work from Roche using the frequency of particular angles found in the CSD for common torsion types [Guba-2016]. Introduced in the 2017.Oct Toolkits Release, this torsion library contains more than 500 new entries and complements the existing library, which is primarily based on an analysis of structures found in the Protein Data Bank (PDB). A new flag,
-torlibtype, has been added to the OMEGA
classicmode that allows users to specify which of the two libraries should be used.
Two new options,
nonmacrocycle, have been added to the
-filterflag of FILTER.
macrocycleis used to remove non-macrocycle molecules in the input file;
nonmacrocycleis used to remove macrocycle molecules.
Four new options,
mmff94smod_Sheff, have been added to both the
-searchffflags of OMEGA
mmff94smodmodifies the torsion interaction parameters of
mmff94sto produce the desired equatorial conformers for monosubstituted cyclohexanes.
mmff94smodterms except Coulomb interactions.
mmff94smod_Truncexcludes both Coulomb interactions and the attractive part of Van der Waals interactions.
mmff94smod terms; the Sheffield solvation model is used during the calculation of energies for the conformers generated.
mmff94smod_NoEstatis now the default for both
A Pan Assay Interference Compounds (
PAINS) filter has been added to the
-filterflag of FILTER by adapting the supplementary material from the original [Baell-2010] paper. The
PAINSfilter can be used as a prefilter set for screening or, more interestingly, as a post-processing filter to identify possible protein-reactive or other assay-confounding functionalities within hits. Any hits so identified will require more care to determine if the measured activity is valid.
Major bug fixes¶
GZfiles are now read correctly when used with
-fixfilewould not be set and the command would proceed as a default OMEGA
Both FLIPPER and OMEGA
classicno longer flip 3D molecules if stereo is defined when using
Minor bug fixes¶
-maxConfRangeis now limited to 1 million to avoid out-of-memory crashes.
FLIPPER now writes out to SMI files. Previously, stereo information was not supported in SMI format.
classicnow fails if an empty torsion library is set to
classicno longer removes zeros at the end of a prefix. For example, the prefix
XXX.00100previously would be expressed as
-SF5groups no longer fail due to the
-typecheckcheck. They may still fail for other reasons.
Support for 64 bit Windows has been added.
32-bit Windows is no longer supported.
Support for Ubuntu 14 and 16 has been added.
Ubuntu 12 is no longer supported.
Support for RedHat v7 has been added.
RedHat v5 is no longer supported.
Support for macOS 10.11, Sierra (10.12), and High Sierra (10.13) has been added.