1470-1-px4nz-BACE_pose_protocol_1B.txt

Name

Similarity/Alignment/Native-Minimization

Software

Rdkit/Torch/Macromodel

System Preparation Parameters

Assumed pH 7
Tautomers considered
OPLS3e charges

System Preparation Method

For each PDB supplied in the stage 1B data package, Maestro's prepwizard was used
to add hydrogens and assign bond orders using using default parameters (pH 7). No minimization was performed.
No waters were removed.

Pose Prediction Parameters

RDKit Morgen Fingerprint (radius=2, bits=1024) Tanimoto similarities
Torch Conformational Hunt Setting - Very accurate and slow #generation of conformers for alignment
Torch Alignment Method - Maximum-common-substructure
Torch MCS Alignment Matching Rule - Very permissive
Torch MCS Alignment Excluded Volume Hardness - Medium
Macromodel force field OPLS3e
Macromodel unconstrained minimization of aligned ligand and all residues (and waters) with 3 Angstroms of the ligand
Macromodel constrained minimization of residues within 6 Angstrom of unconstrained atoms

Pose Prediction Method

For each of the 20 query ligands the most similar BACE-bound ligand in the PDB was identified as
an alignment reference using the RDkit Morgan fingerprints. Each query was aligned to its reference ligand using a maximum
common substructure alignment in Torch. The aligned query was then merged into its native protein structure (with any waters)
provided as part of the stage 1B data package. Energy minimized was performed on the ligand keeping the protein structure
frozen.

Answer 1

No