GRID-Based Three-Dimensional Pharmacophores I: FLAPpharm, a Novel Approach for Pharmacophore Elucidation

• DOI: 10.1021/ci300153d
• Publication Date: 2012-09-12T12:47:45Z
• Authors: Simon Cross; Massimo Baroni; Laura Goracci; Gabriele Cruciani
• Keywords: Benchmark (surveying)

Pharmacophore elucidation approaches are routinely used in drug discovery, primarily with the aim of determining three-dimensional arrangement common features shared by ligands interacting at site interest; these can then be to investigate structure-activity relationship between and also screen for other molecules possessing relevant features. Here we present a novel approach based on GRID molecular interaction fields derivative method FLAP that has been previously described, which provides reference framework compare both small molecule macromolecular protein targets. Unlike classical pharmacophore extract simplistic features, determine those across data set, use align structures, FLAPpharm first aligns structures subsequently extracts terms their fields, pseudofields, atomic points, representing as more comprehensive pharmacophoric pseudomolecule. The is applied number sets performance reproducing X-ray crystallography-based alignment, its discriminatory ability when virtual screening illustrate explain alternative binding modes. In part two this publication, benchmark set presented discussed.