ICM/APF 3D QSAR
Molsoft ICM 3.8-5
default
Standard ICM VLS Scoring function was used. ICM VLS Score is a GBSA-type scoring function augmented with a directional hydrogen bonding/metal coordination term and optimized for active/inactive ligand discrimination.
ICM Dock
Molsoft ICM 3.8-5
default
Standard ICM conversion procedure was used to add hydrogens, assign atom types and charges
All the waters were removed.
Monte Carlo search 'effort' parameter was set to 10.
Docking runs were executed with the above specified parameters while default values
were applied for the rest of the variables. Each ligand was docked to a set of receptor conformations from X-ray structures in PDB.
Only poses with APF (Atomic Property Fields) similarity >0.4 to the cognate ligand of the corresponding receptor conformation were retained.
The top 5 poses according to ICM VLS score were further analysed: poses were re-ranked according to composite ICM-VLS/APF score (the product of physics-based ICM VLS Score and APF similarity to the cognate ligand of the respective receptor conformation). Poses were also clustered across the compound set to identify consensus poses for each chemotype (when applicable). In a few cases where best-scoring pose disagreed with the chemotype consensus, the pose in agreement with the chemotype was selected instead.