The document discusses using "fake ligands" as reference compounds for ligand-based virtual screening methods like ROCS. A fake ligand is generated by mapping solvent clusters onto the binding site of a protein structure, complementing its shape and properties. Using fake ligands as queries for ROCS yielded similar performance as using crystalized ligand structures from X-ray data. This fake ligand concept can generate reference compounds for ligand-based screening without needing a known binding molecule.

1. The Fake Ligand Concept
David Hall and Istvan Enyedy

2. Ligand-Based Methods are Fast
211 Million
Conformers
(2 Million
Cmpds)
ROCS
Fast ROCS
12x3.4 GHz Cores
2304 Cores
3D Similar
Compounds
120 Min
<3 Min
2xK5200

3. ROCS and FastROCS
Database
ROCS, Fast
ROCS
3D Similar Compounds
Reference Ligand
ROCS query

4. Can We Generate a Reference Compound
From the Structure of a Binding Site?
Protein Structure Virtual reference compound

5. Solvent Mapping to Generate Ligands
That Complement the Binding Site
Fragment clusters
Fake ligand
Protein Structure
ATLAS Ligand
ATLAS,
Acpharis
ROCS Query
Future Medicinal Chemistry 2016, 8, 1815-1823

6. ROCS. Using Fake Ligands as Queries is
Comparable to Using X-Ray Ligands
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ROCAUC
Target
X-Ray
Fake Ligand