Abstract
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.
Financial & competing interests disclosure
DR Hall is the CEO of Acpharis, which developed and sells the Atlas software discussed in the article. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.