MMS CrossDocking - Protein APO (PAPO) Method 2


Maestro 2016/DockBench 1.01 [1]/Autodock 6.5/GOLD 5.4.1/MOE 2015.1001/Plants 1.2/RDock 2013.1

System Preparation Parameters

Assumed pH 7.4

System Preparation Method

Ligands were prepared using LigPrep Tool of Maestro, retaining specified chiralities and without tautomers generations. Strong acids were deprotonated and strong bases protonated using Wash tool of MOE. Ligands were minimized with MMFF94 force field.
Proteins were prepared by selecting chain A of crystallographic structures and by using Structure Preparation Tool of MOE. Protonation states were assigned with Protonate 3D tool of MOE.

Pose Prediction Parameters

CrossDocker Num_poses= 20
CrossDocker Radius= 20
CrossDocker proteins pdb (21 pdbs) = 3bej,3dct,3dcu,3fli,3fxv,3dg2,3hc5,3hc6,3oki,3olf,3omk,3omm,3oof,3ook,3p88,3p89,3rut,3ruu,3rvf,4qe6,4qe8
CrossDocker docking protocols= autodock-ga,autodock-lga,autodock-ls,glide-sp,gold-asp,gold-chemscore,gold-goldscore,gold-plp,moe-affinitydg,moe-gbviwsa,moe-londondg,plants-chemplp,plants-plp,plants-plp95,rdock-solv,rdock-std
Key parameters of the docking protocols are specified in DockBench manuscript [1].

Pose Prediction Method

Crystallographic structures of FXR were retrived from the PDB and used for a cross-docking benchmark. The aim of the cross docking benchmark was to identify which was the "docking protocol" that was able to better reproduce each co-crystalized conformation of the ligands.
The evaluation of the docking protocols performances in reproducing the crystallographic ligand conformation was performed by computing the RMSD of the docking poses to the references. For each docked ligand on each protein, the RMSD average of the top five poses was computed. For each protein, the average of the average-top-5-values of all docked ligands was used as score. In the cross docking approach, the self-ligand (belonging to the self-crystal structure) was excluded from the ligands subset considered in the calculation of the final RMSD.

Gold-goldscore was identified as the best "docking protocol" considering the minimum RMSD gained by this protocol in the cross-docking job.

Differently by the other submission, we decided to use the protein structure proposed by the organizers.

FXR1 to FXR36 ligands were docked to the proposed protein using gold-goldscore. The VirtualScreening tool of the DockBench software was employed. The top 5 highest-score poses for each ligand were selected for the submission.

[1] Cuzzolin, A.; Sturlese, M.; Malvacio I.; Ciancetta, A.; Moro S. DockBench: An integrated Informatic Platform Bridging the Gap between the Robust Validation of Docking Protocols and Virtual Screening Simulations. Molecules 2015, 20 (6), 9977-9993.