The use of fake ligands from computational solvent mapping in ligand and structure-based virtual screening.

AIM: Virtual screening selects compounds that resemble a known modulator or compounds that fit into the binding site of a target protein. Computational solvent mapping defines important chemical features for binding to a target protein. Results/methodology: We have tested the ability to use solvent mapping for generating a 'fake' ligand that is a negative image of the binding site. We used this fake ligand as a query for the program ROCS and to define the search space of the docking programs FRED and HYBRID.

CONCLUSION: The fake ligands perform comparably to or better than the ligands from crystal structures across a set of ten targets. Thus, the approach is suitable for guiding virtual screening and hit-to-lead optimization.