Rhodium 5.8 HTS
Pymol 1.2
Accelerys Discovery Studio 2.0
Rhodium 5.8
OpenBabel 2.3.90
Caesar 3D Conformers with Default Parameters
Pymol was used to add hydrogens to crystal structures using default parameters.
All the waters were removed.
Ligand conformational libraries were generated using the Casear method in Discovery Studio 2.0 with default parameters, for all but two ligands.
All conformers were used in the docking. BACE_2 and BACE_3 were created from SMILES strings using OpenBabel 2.3.90, and optimized with the obminimize program. PDB files were unmodified except for the addition of hydrogen atoms.
Rhodium HTS Default Parameters
Grid Resolution 1.7 #exhaustiveness of global search (default=2.0)
NumPoses 144 #max number of poses to generate
Docking runs were executed with the above specified parameters, using approximately 50 crystal structures of BACE.
Structures were selected based on docking score, considering all poses in all crystal structures.
The topmost-scoring pose of each ligand from the Rhodium docking is submitted with this protocol.
No
Yes
Rhodium HTS
Accelerys Discovery Studio 2.0
Pymol 1.2
Rhodium 5.8
Docking grid resolution 1.7
Refined poses 144
Approximately 50 crystal stuctures for BACE were downloaded from the Protein Data Bank.
We used Pymol to add hydrogens and remove waters from all crystal structures. Ligand conformers were
generated with the Discovery Studio 2.0 Caesar conformer method, with default parameters, starting from SMILES strings.
Docking was performed with Rhodium 5.8, using all ligand poses in all crystal structures. For each ligand, the best scoring pose
by a ligand re-scoring was selected as the basis for the ligand ranking. The re-scoring is based on a regression model derived from structures and affinities from the SCORPIO database which features direct affinity (K_d) measurements from calorimetry.
No
No