id-6_200x32M_noxraywat_adadelta_drylig_yesfilter_nobias
OpenCLAutoDock/AutoDock4.2/OpenBabel/Python/Reduce
Assumed pH 7.4, single protonation state
Gasteiger charges for both ligand
Macrocycles broken
6-member ring in ligand BACE_13 modeled as two rigid conformations
X-ray waters removed from protein
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.
Hydroxyl groups are considered disordered.
200 Genetic Algorithm (GA) instances
32 million energy evals per GA
Local search frequency: 100 percent
Local search max evals: 500
Local search method: Adadelta
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 ligand BACE_5, no pose passed the filters, so we
submitted the pose with the best score.
No
Yes