Name

100x10M_noxraywat_adadelta_drylig_yesfilter_yesbias

Software

OpenCLAutoDock/AutoDock4.2/OpenBabel/Python/Reduce

System Preparation Parameters

Assumed pH 7.4, single protonation state
Gasteiger charges for both ligand and protein
Macrocycles broken

System Preparation Method

Ligands protonated at standard pH using OpenBabel based scripts.
Only one protonation state is considered. The large macrocyclic substructures of ligands
are broken to allow conformational sampling during the docking.
Proteins protonated with reduce, single protonation state.
X-ray waters are removed from proteins.

Pose Prediction Parameters

100 Genetic Algorithm (GA) instances
10 million energy evals per GA
Local search frequency: 100 percent
Local search max evals: 500
Local search method: Adadelta

Pose Prediction Method

Ligands were docked onto 11 protein structures chosen to
cover multiple conformations of the binding pocket
(2b8v, 2f3f, 2p4j, 2wf3, 3l59, 3msj, 3msk, 4weo, 4fs4, 4rcf, 5hu0).
Macrocyclic ligands were docked in an open conformation and
a linear potential was used to bring the broken bond back together (50 kcal/mol/angstrom).
The scoring function was biased to penalize docking poses that differ from the x-ray
coordinates of ligand 4dpf, with respect to atoms O15, N16 and C18.
The penalty was applied to atoms further than 1.2 angstroms from the corresponding
reference atom (either O15, N16 or C18 in 4dpf).
Every pose was subjected to post-processing filters to evaluate similarity with known
binding modes - we refer to these filters as substructure filters.
The following smarts strings and associated reference ligands were considered:
4dpf, [CX4][CX4]([OH1])[CX4][NX3][CX3]=O
2f3f, [CX4][NX3][CX3](=[O])[CX4]([CX4])[CX4][CX4]([OH1])[CX4][NX3][CX3]=O
4dpf, [CX4][N][CX4][CX4]([OH1])[CX4][NX3][CX3]=O
4dpf, [CX4][c][c][c][CX4][N][CX4][CX4]([OH1])[CX4][NX3][CX3]=O
4dpf, [CX4]([OH1])[CX4][NX3][CX3](=O)[a]1[a][a][a][a][a]1
2f3f, [CX4]([OH1])[CX4][NX3][CX3](=O)[CX4][NX3][CX3](=[O])[CX4]
4k8s, [CX4]([OH1])[CX4]([CX4][a]1[a][a][a][a][a]1)[NX3][CX3](=O)
Among the poses passing the substructure filters, which may have been docked
in any of the 11 receptors, the pose with the
lowest AutoDock4.2 energy is considered as the correct pose.

Answer 1

No

Answer 2

Yes

Name

autodock42_energy

Software

OpenCLAutoDock/AutoDock4.2

Parameters

Assumed pH 7.4, single protonation state
Gasteiger charges for both ligand and protein

Method

Ligands were docked according to pose prediction protocol named 100x10M_noxraywat_adadelta_drylig_yesfilter_yesbias.
Ligands are ranked according the AutoDock4.2 scoring function.

Answer 1

No

Answer 2

No