When using a conformer lacking the Met909-based pocket (PDBid: 1ZUC), 2 could only be placed in position 920.
The dataset of 2643 molecules was downloaded from the CDD Public Access (https://www.collaborativedrug.com/pages/public_access) as an sdf and then a 3D database was created in Discovery Studio using FAST conformer generation with up to 255 conformations.
The dataset of 2311 molecules was provided by Microsource (http://www.msdiscovery.com/spectrum.html) as an sdf and then a 3D database was created in Discovery Studio using FAST conformer generation with up to 255 conformations.
Using the Balloon conformer generation, we could generate 3D coordinates and inspect the screening hits in 3D using the Jmol component in Bioclipse.
Conformations of all the inhibitors were generated by using the "Best conformer generation" with 20.0 kcal/mol as energy cutoff, and maximum number of conformers was selected 255, while all other parameters were set to default, except the Uncert value of 3.0 for all the compounds.
The FXR ligand structures from recent literature were created using ChemBioDraw Ultra 11.0 (www.cambridgesoft.com) and converted into 3D multiconformational SD files using the FAST conformer generation algorithm of DiscoveryStudio 2.5.
In this paper, we study a number of the software programs currently being used in conformer generation, analyzing their ability to regenerate known ligand binding conformations.
(3) Molecules with a non-organic element were not included because they are not compliant with the 94 s variant of the Merck molecular force-field (MMFF94s), which was used for conformer generation (without coulomb interaction terms).
Effects of different settings for three important parameters (the fragment sampling rate, the type of the molecular force field, and the size of the energy window) that OMEGA uses for conformer generation were investigated to find their optimal settings.
The toolkit used for conformer generation, alignment of conformers, and RMSD calculation produced the non-symmetry matrix (but approximate symmetric) resulting from (1) selection algorithm of starting position for the alignment (inertial frame alignment algorithm), (2) rigidity of reference conformer during finding 'centers-of-mass', and (3) single selection from multiple OEBestOverlay results.
