Omega.parm: Difference between revisions
Jump to navigation
Jump to search
Oliv Eidam (talk | contribs) No edit summary |
No edit summary |
||
| (4 intermediate revisions by one other user not shown) | |||
| Line 22: | Line 22: | ||
omega.SetEnergyWindow(12.5) | omega.SetEnergyWindow(12.5) | ||
omega.SetMaxConfs(600) | omega.SetMaxConfs(600) | ||
omega.SetRMSThreshold(0.80) | omega.SetRMSThreshold(0.80) | ||
omega.SetBuildForceField('mmff94s_NoEstat') | omega.SetBuildForceField('mmff94s_NoEstat') | ||
omega.SetSearchForceField('mmff94s_NoEstat') | omega.SetSearchForceField('mmff94s_NoEstat') | ||
| Line 32: | Line 29: | ||
*you could increase the energy window: e.g. omega.SetEnergyWindow(25.0) | *you could increase the energy window: e.g. omega.SetEnergyWindow(25.0) | ||
=> There is no benchmarking of this setting that I am aware of... | => There is no benchmarking of this setting that I am aware of... | ||
*you could increase the number of output conformations: e.g. omega.SetMaxConfs(10000) | *you could increase the number of output conformations: e.g. omega.SetMaxConfs(10000) | ||
=> Molecules in ZINC have a | => Molecules in ZINC have a cutoff at 600 conformations, which is certainly on the low side for flexible ligands | ||
*you could lower the RMS threshold between the confs: e.g. omega.SetRMSThreshold(0.40) | *you could lower the RMS threshold between the confs: e.g. omega.SetRMSThreshold(0.40) | ||
=> This results in finer sampling of conformational space | => This results in finer sampling of conformational space | ||
*you could change the force field to included electrostatics: e.g. omega.SetBuildForceField('mmff94s') and omega.SetSearchForceField('mmff94s') | *you could change the force field to included electrostatics: e.g. omega.SetBuildForceField('mmff94s') and omega.SetSearchForceField('mmff94s') | ||
=> Internal benchmarkings on DUDE (by RGC) have shown that electrostatics improves enrichment for many targets. And for ligands exhibiting internal salt bridges, it may be essential to include electrostatics during conformation generation, as shown below in the example of re-docking the S1P1R ligand. | => Internal benchmarkings on DUDE (by RGC) have shown that electrostatics improves enrichment for many targets. And for ligands exhibiting internal salt bridges, it may be essential to include electrostatics during conformation generation, as shown below in the example of re-docking the S1P1R ligand. | ||
| Line 42: | Line 42: | ||
===Example of omega.parm=== | ===Example of omega.parm=== | ||
[[File:Dock4 noEstat.png|thumb|right|alt=Comparison of crystal pose (green) to docked S1P1R ligand (cyan) with electrostatics turned off during conformation generation. No salt bridge between phosphonate and amine, score=-3. |Comparison of crystal pose (green) to docked S1P1R ligand (cyan) with electrostatics turned off during conformation generation. No salt bridge between phosphonate and amine, score=-3.]] | [[File:Dock4 noEstat.png|thumb|right|alt=Comparison of crystal pose (green) to docked S1P1R ligand (cyan) with electrostatics turned off during conformation generation. No salt bridge between phosphonate and amine, DOCK score=-3. |Comparison of crystal pose (green) to docked S1P1R ligand (cyan) with electrostatics turned off during conformation generation. No salt bridge between phosphonate and amine, DOCK score=-3.]] | ||
[[File:Omega1.png|thumb|right|alt=Comparison of crystal pose (green) to docked S1P1R ligand (yellow) with electrostatics turned on during conformation generation. Nice salt bridge between phosphonate and amine, score=-30. |Comparison of crystal pose (green) to docked S1P1R ligand (yellow) with electrostatics turned on during conformation generation. Nice salt bridge between phosphonate and amine, score=-32.]] | [[File:Omega1.png|thumb|right|alt=Comparison of crystal pose (green) to docked S1P1R ligand (yellow) with electrostatics turned on during conformation generation. Nice salt bridge between phosphonate and amine, DOCK score=-30. |Comparison of crystal pose (green) to docked S1P1R ligand (yellow) with electrostatics turned on during conformation generation. Nice salt bridge between phosphonate and amine, DOCK score=-32.]] | ||
# Example omega toolkit configuration file | # Example omega toolkit configuration file | ||
| Line 81: | Line 81: | ||
# Omega file with special no ring conformation parameters | # Omega file with special no ring conformation parameters | ||
SetMaxConfs(30) | SetMaxConfs(30) | ||
==Acknowledgments== | |||
Thanks to MM and RGC. | |||
[[Category:Manual]] | |||
[[Category:Software]] | |||
[[Category:Conformational modeling]] | |||
Latest revision as of 04:10, 14 February 2014
Changing settings for OMEGA (OpenEye)
You may be interested to change the default settings for OMEGA (defined in omega.py) when generating conformations for docking. Mabye you want to increase the number of conformations sampled per ligand, or the force field used.
The best way to change the settings for OMEGA is to copy a file called omega.parm into the directory where you want to generate ligand conformations using dbgen.csh. You should find a template in $DOCK_BASE/data/omega.parm
1) Copy omega.parm in your working directory:
cp $DOCK_BASE/data/omega.parm .
(=> if your ligand has no rings, copy and edit omega_noring.parm ($DOCK_BASE/data/omega_noring.parm)
2) Edit and save omega.parm (using the same name) in your favorite editor.
3) Run dbgen.csh with altered settings in omega.parm (has to be in directory where you run dbgen.csh):
dbgen.csh my_ligs.smi
Increase ligand conformation sampling or change the type of force field
An example of omega.parm is shown at the bottom of this page. Settings you may want to consider changing are:
omega.SetEnergyWindow(12.5)
omega.SetMaxConfs(600)
omega.SetRMSThreshold(0.80)
omega.SetBuildForceField('mmff94s_NoEstat')
omega.SetSearchForceField('mmff94s_NoEstat')
- you could increase the energy window: e.g. omega.SetEnergyWindow(25.0)
=> There is no benchmarking of this setting that I am aware of...
- you could increase the number of output conformations: e.g. omega.SetMaxConfs(10000)
=> Molecules in ZINC have a cutoff at 600 conformations, which is certainly on the low side for flexible ligands
- you could lower the RMS threshold between the confs: e.g. omega.SetRMSThreshold(0.40)
=> This results in finer sampling of conformational space
- you could change the force field to included electrostatics: e.g. omega.SetBuildForceField('mmff94s') and omega.SetSearchForceField('mmff94s')
=> Internal benchmarkings on DUDE (by RGC) have shown that electrostatics improves enrichment for many targets. And for ligands exhibiting internal salt bridges, it may be essential to include electrostatics during conformation generation, as shown below in the example of re-docking the S1P1R ligand.
Example of omega.parm
# Example omega toolkit configuration file
# File Parameters
SetCommentEnergy(False)
SetIncludeInput(False)
SetRotorOffset(True)
SetSDEnergy(False)
SetWarts(True)
# 3D Construction Parameters
SetBuildForceField('mmff94s_NoEstat')
SetCanonOrder(True)
SetFixDeleteH(True)
SetDielectric(1.0)
SetExponent(1.0)
SetFixRMS(0.15)
SetFromCT(False)
SetFixMaxMatch(1)
SetFixUniqueMatch(True)
# Structure Enumeration Parameters
SetEnumNitrogen(False)
SetEnumRing(False)
# Torsion Driving Parameters
SetEnergyWindow(12.5)
SetMaxConfs(600)
SetMaxRotors(-1)
SetMaxSearchTime(120.0)
SetRangeIncrement(5)
SetRMSThreshold(0.80)
SetSearchForceField('mmff94s_NoEstat')
SetTorsionDrive(True)
Example of omega_noring.parm
# Omega file with special no ring conformation parameters SetMaxConfs(30)
Acknowledgments
Thanks to MM and RGC.