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

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.

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.