MOE contains the industry-leading
suite of pharmacophore discovery applications used for fragment-, ligand- and
structure-based design projects. Pharmacophore modeling is a powerful
means to generate and use 3D information to search for novel active
compounds, particularly when no receptor geometry is available. Pharmacophore
methods use a generalized molecular recognition representation and
geometric constraints to bypass the structural or chemical class bias of 2D
Construct queries with an easy-to-use interactive
query editor using either proteins or ligands. Use the query to screen
a conformational database to determine candidate active compounds that satisfy
the pharmacophore model. Customize pharmacophore annotations with SMARTS
chemical patterns and Boolean expressions. Restrict shape
(receptor or ligand) with volume constraints and refine the query with directional
vector constraints, centroids of atoms, or partial matches on
annotations. Apply MOE’s active site analysis tools help identify key
interactions of molecular recognition.
pharmacophore queries and induced molecular alignments from a collection
of input compounds (possibly with activity data) by considering all
possible discrete geometries and all possible combinations of feature query
expressions. Enforce limits on feature counts and add custom query
expressions. Score queries based on known active compound coverage,
statistical activity enrichment and atomic overlap of matching
conformations. Protein Ligand Interaction Fingerprints (PLIF) can
automatically generate queries from bound ligands given a set of aligned
complexes (or docking results).
Construct 3D conformation databases
for virtual screening from SD files or SMILES strings using MOE's parallelized High
Throughput Conformational Search application. Prepare compound
collections with sdtools for duplicate removal, tautomer and ionization state
and stereo enumeration, fragment generation, and property filtering.
CCG provides a large lead-like whole molecule 3D database and a large fragment
database derived from vendor catalogs and medicinal chemistry literature.
Rapidly screen a conformational
database for compound conformations that satisfy a pharmacophore query. Search
multiple databases, a sub-range of molecules or a database of docked
compounds. Search MOE MDB, or Omega OEB files directly. Output
data consists of molecules that satisfy the 3D pharmacophore query (either all
conformations or just the conformations that satisfy the query). Partial
matches, SMARTS patterns, output of all symmetric matches and
specification of essential features are supported. Screen corporate
collections in minutes on a compute cluster.
and replace [Grimshaw 2010] ligand scaffolds (with or
without the receptor). Medicinal chemistry transformations perform
small isosteric changes to a molecule rely on reaction transformations
(.rxn) that are generated using standard sketchers. CCG provides a
database of 170+ transformations. Refine coordinates in the
active site if available (flexible receptor) and calculate binding
scores while retaining pharmacophore features. Apply 2D and
3D descriptor filters, QSAR and fingerprint models.
[Deschenes 2007] Deschenes, A., Sourial, E.; Ligand
Scaffold Replacement using MOE Pharmacophore Tools.; JCCG (2007)
Grimshaw, S.; Scaffold Replacement in MOE; JCCG (2010)
[Labute 2001] Labute, P., Williams,
C., Feher, M., Sourial, E., Schmidt, J. M.; Flexible Alignment of Small
Molecules; J. Med. Chem. 44 (2001) 1483–1490.