y0048-LigandScoringProtocol.txt

Name

ICM/APF 3D QSAR

Software

Molsoft ICM 3.8-6

Parameters

default

Method

Activity data for compounds with Tanimoto similarity > 0.6 to any of the challenge ligands were extracted from ChEMBL V2.3
ChEMBL compounds were docked using the same protocol as for challange ligands.
The challenge ligands were clustered by Atomic Property Fields (APF) 3D similarity using their docked poses at a distance cutoff of 0.5
For each cluster, a custom ICM-score/3D APF QSAR model was built using a subset of the most similar compounds in the ChEMBL training set based on 3D APF similarity of docked poses.
The models were built using a two stage approach to encorporate both physical terms as well as knowledge-based chemical 3D APF similarity:
First level model was constructed using regular 3D APF QSAR, while second level model combined first level prediction and 6 physical terms from ICM scoring function in a random forest regression.
pKd for each challange compound was predicted using the model corresponding to its cluster. pKd were converted to binding energies.

Answer 1

no

y0048-PosePredictionProtocol.txt

Name

ICM Dock

Software

Molsoft ICM 3.8-6

System Preparation Parameters

standard

System Preparation Method

Standard ICM conversion procedure was used to add hydrogens, assign atom types and charges.

Pose Prediction Parameters

Monte Carlo search 'effort' parameter was set to 20.

Pose Prediction Method

Four representative pdb entries 1YWN 3B8Q 3B8R 3CP9 were selected for receptor conformation ensemble based on the ability to recover near-native docking poses for most available PDB ligand complexes.
All ligands were docked using standard ICM-dock protocol using '4D' mode to encorporate receptor conformation ensemble. Co-crystallized ligands were used for Atomic Property Field (APF) bias.
3 independent runs were performed, retaininng 10 top poses for the total of 30 poses per ligand.
For each ligand, best pose was selected accoridng to a composite score calculated as a sum of normalized ICM docking (physical) score and normalized APF 3D similarity to co-crystallized ligands.

Answer 1

No

Answer 2

Yes