Structure-guided Docking using Glide
Open Babel 2.3.2/UCSF Chimera 1.11.2/Maestro Version 11.1.011
Assumed pH 7.4
MMFF94 force field for generation of 3D structure of the ligands.
Gasteiger charges
1. The ligands were protonated using OpenBabel 2.3.2 at pH 7.4.
2. MMFF94 force field was used to generate the 3D conformation of each ligand GUI version of Open Babel.
3. Docking was performed using crystal structures provided in the stage 1b. Prior to docking, water molecules and other heteroatoms were deleted and structure was processed using Protein Preparation Wizard in Maestro. Incomplete side chains were corrected.
4. The protonation state of the residues were adjusted according to pH 7.4.
5. To define the binding site and to generate grid for molecular docking following parameter were used
GRID_CENTER -3.84, 5.90, -5.37
INNERBOX 10, 10, 10
OUTERBOX 30, 30, 30
Glide SP protocol
Ligands were treated flexible. Enhanced sampling and Post-docking minimization was opted. For each ligand 45 docked conformations were generated.
Glide gscore (empirical)
Molecular docking of all ligands was performed using Glide module provided in Maestro. Before docking of 24 ligands, redocking of inhibitor bound to the crytal structure of human Cathepsin S (PDB ID:3KWN) was carried out. Due to large number of rotatable bonds in the ligands, 45 docked poses of each ligand were generated. Pose selection was based on glide gscore and comparison of interactions with the inhibitor bound crystal structure of human Cathepsin S. Selecetd poses are not necessarily the top scoring poses.
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