Format

Send to

Choose Destination
J Comput Aided Mol Des. 2012 Mar;26(3):319-27. doi: 10.1007/s10822-012-9558-x. Epub 2012 Mar 7.

A reverse combination of structure-based and ligand-based strategies for virtual screening.

Author information

1
Departamento de Farmacología, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain.

Abstract

A new approach is presented that combines structure- and ligand-based virtual screening in a reverse way. Opposite to the majority of the methods, a docking protocol is first employed to prioritize small ligands ("fragments") that are subsequently used as queries to search for similar larger ligands in a database. For a given chemical library, a three-step strategy is followed consisting of (1) contraction into a representative, non-redundant, set of fragments, (2) selection of the three best-scoring fragments docking into a given macromolecular target site, and (3) expansion of the fragments' structures back into ligands by using them as queries to search the library by means of fingerprint descriptions and similarity criteria. We tested the performance of this approach on a collection of fragments and ligands found in the ZINC database and the directory of useful decoys, and compared the results with those obtained using a standard docking protocol. The new method provided better overall results and was several times faster. We also studied the chemical diversity that both methods cover using an in-house compound library and concluded that the novel approach performs similarly but at a much smaller computational cost.

PMID:
22395903
DOI:
10.1007/s10822-012-9558-x
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center