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Research Article

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

    David R Hall

    *Author for correspondence:

    E-mail Address: david@acpharis.com

    Acpharis, 160 N Mill St, Holliston, MA, USA

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    &
    Istvan J Enyedy

    Biogen, 14 Cambridge Center, Cambridge, MA, USA

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    Published Online:15 Sep 2016https://doi.org/10.4155/fmc-2016-0115

    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.

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