1470-1-80zep-id-12_100x10M_sphericxraywat_adadelta_wet_yesfilter_nobias.txt

Name

id-12_100x10M_sphericxraywat_adadelta_wetlig_yesfilter_nobias

Software

OpenCLAutoDock/AutoDock4.2/OpenBabel/Python/Reduce

System Preparation Parameters

Assumed pH 7.4, single protonation state
Gasteiger charges for both ligand and receptor
Explicit waters on ligand
Macrocycles broken
X-ray waters kept in protein

System Preparation Method

Ligand protonated at standard pH using OpenBabel based scripts.
Only one protonation state is considered. The large macrocyclic substructures of ligands
1-19 are broken to allow conformational sampling during the docking.
Protein protonated with reduce, single protonation state.
X-ray waters of the protein are modeled as spherical, i.e. they have both HB donor and acceptor
capabilities, orientation of water hydrogens is irrelevant.
Similarly, hydroxyl groups are considered disordered.
Explicit waters are added to ligand along hydrogen bond vectors.

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

Macrocyclic ligands are docked in an open conformation and
a linear potential is used to bring the broken bond back together (50 kcal/mol/angstrom).
Every pose is subjected to post-processing filters to evaluate similarity with known
binding modes. 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)
All poses (up to 5) passing similarity filters are submitted for evaluation.
The ranking of the poses is provided by the AutoDock4.2 scoring function.
Exceptionally, for ligands BACE_5, BACE_11 and BACE_19 no pose passed the filters,
so we submitted the pose with the best score.

Answer 1

No

Answer 2

Yes