LigandMatch
LigandMatch 1.0
OpenBabel 2.3.90
Default 3D pose generation with babel, structure minimization with MMFF94 forcefield and 20000 steps
The ligand from PDB 3L5E was extracted from the file and used as a matching template. Contest ligand geometries
were created with OpenBabel from the provided SMILES strings, and structures were minimized with obminimize from the OpenBabel package.
Number of trial poses minimized was 32
Ligands were aligned with the 3L5E ligand as a template, using a primitive square well potential with an attractive component only, as a rough screen, and then refined minimizing the distance between all atom pairs.
No
Yes
Rhodium HTS
OpenBabel 2.3.90
Rhodium ver. 6.25
N/A
A 2-parameter linear regression model, trained on a published SAR dataset by Hanessian, et al., was developed using
Rhodium docking poses of a user-selected training set (see below) docked in the 2F3E BACE crystal structure. The 3D geometries of the ligands were created
with OpenBabel 2.3.90 from the provided GC4 SMILES strings (or BindingDB dataset) and optimized with the MMFF94 forcefield (n=20000 steps)
with the Oboptimize program. Multiple conformers were generated with the OpenBabel GA conformer generator, using standard parameters.
The regression independent variables from training set docking were 1) count of hydrophobic atoms in the ligand and 2) ligand binding position, with the
distance between the pose center of mass and co-crystallized holo ligand center of mass, squared, as the other parameter.
The pose closest to the center of mass, rather than the topmost-scoring pose, was used in the evaluation for
for predicting IC50s. This regression model was applied to the to the GC4 BACE score prediction set, creating ligand-based prediction scores.
TRAINING SET REFERENCE:
(2) Dataset as found in BindingDB.org from Hanessian S, Yang G, Rondeau JM, Neumann U, Betschart C, Tintelnot-Blomley M.
Structure-based design and synthesis of macroheterocyclic peptidomimetic inhibitors of the aspartic protease beta-site amyloid precursor protein cleaving enzyme (BACE).
J Med Chem. 2006 Jul 27;49(15):4544-67.
No
No