Alignment/AlphaSpace/Smina
RDKit(2018.3.3)/Smina(2017.4.29)/MGLTools(1.5.6)/OpenBabel(2.4.1)/AlphaSpace(1.1.10)/PDB2PQR(2.1.0)
pdb2pqr --ff=amber --ph-calc-method=propka --with-ph=5
1. Receptor preparation: PDB2PQR was used to calculate receptor protonation states and hygrogen atoms are added accordingly. 2. Ligand preparation: a. Conformer library was generated using RDKit. b. Ligand protonation states were calculated using in-house script, which was developed by functional group potonation states at specific conditions. 3.Ligand and receptor pdbqt files are prepared by MGLTools.
smina --minimize --minimize_iters=100
1. Morgan fingerprints were used to select most similar cocrystal ligand for each GC4 compound. 2.Generated conformers were aligned to its most similar cocrystal ligand using MCS (Most Common Substructures) in RDKit. 3. Aligned conformers were local minimized against its most similar cocrystal ligand's receptor using Smina. 4. AlphaSpace was used to analyze available CatS crystal structures in PDB, and major pocekts were determined by AlphaSpace pocket space and ligandability. 5.Minimized conformers were filtered by their major pocket space occupancy 6. Top Smina score conformer was selected as predicted pose.
No
Yes
DeltaVinaFragXGB_C
chimera(Version 1.10.2)/xgboost(Version 0.80)/RDKit(Version 2018.03.3)/python(Version 3.6.3)/MSMS(Version 2.6.1)/MGLTools(Version 1.5.6)/OpenBabel(Version 2.4.1)/AutoDock Vina(Version 1.1.2)
no explicit water included
We used DeltaVinaFragXGB_C scoring function to rescore selected poses based on pose selection protocol Alignment/AlphaSpace/Smina. DeltaVinaFragXGB is a novel machine learning scoring function trained on PDBbind(v2016) and CSAR datasets via XGBoost and delta Vina parameterization. It incorporates features related to ligand conformation stability, explicit mediating water molecules and ligand fragments. DeltaVinaFragXGB_C was validated using a time-split dataset based on PDBbind and GC3 CatS dataset.The detailed approach will be published in upcoming paper.
No
Yes