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Because FlexX relies on an incremental build-up scheme for docking, the ligand is split into pieces at rotatable bonds prior to docking. Problems in this context are flexible ring conformer structures: Here, there may be a multitude of conformational minima which should be treated during docking. Therefore, the ring conformer generation by itself is not a trivial task – which is why we rely on third party software to generate the necessary structures. (Please be advised that usually these tools require a separate license from each individual distributor, please see below.) Once configured, FlexX will automatically trigger this tool and you will only obtain your docking results.
In principle, any 3D ring conformer generator program can be used with FlexX docking. FlexX has been developed in parallel with CORINA, and this is our personal recommendation. Through the SYBYL interface customers will have traditionally used CONFORT. However here, we will mainly concentrate on how to set up and use CORINA with FlexX to deal with stereo centers in ligands.
Because of the differences in ring conformer generators, please note that different 3D conformer generation programs will give different docking results. They may even differ if only different versions of the same tool are used!
CORINA is available through Molecular Networks GmbH, however we can provide you with CORINA_F which is a low cost feature-limited version of CORINA that is specifically designed to do the FlexX specific tasks.
The type of conformer generation used can be defined in FlexX's master configuration file, config.dat by changing the RING_MODE parameter:
0 for rigid ring systems,
1 for CORINA, and
2 for CONFORT,
i.e., in the config.dat section below, it is set for CORINA:
# Ligand flexibility handling
RIGID_TORSIONS 0
RING_MODE 1
TORSION_MODE 0
The correct path of your executable of the conformer generation program has to be defined in the @programs section in config.dat at the keyword RCGENERATOR, which is an abbreviation of ring conformation generator. This is dependent on the platform you are using, Linux, Windows, SGI etc. Here is an example for the Linux platform:
# Intel based PCs with Linux
#system Linux
FLEXX bin/flexx-2.1.0-Linux
FLEXV /software/BioSolveIT/flexv/bin/flexv -size 900 750 -pos 400 400
RCGENERATOR ../ext_tools/corina/Linux/corina -d flexx
3DGENERATOR ../ext_tools/corina/Linux/corina -i t=sdf,dummies -o t=sdf,m2l
#end_system
Also visible in the example is the input parameters to CORINA. (Advanced parameters for CORINA can be called with corina -h all).
If you have troubles with your ring conformer generation step, you can check CORINA's output files: The parameter KEEP_RCGEN_FILES can be set to 1, so all temporary IO files are saved for viewing. Certainly, we are always happy to help through the support page.
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