title: Atom pair 2D-fingerprints perceive 3D-molecular shape and pharmacophores for very fast virtual screening of ZINC and GDB-17.
abstract: Three-dimensional (3D) molecular shape and pharmacophores are important determinants of the biological activity of organic molecules; however, a precise computation of 3D-shape is generally too slow for virtual screening of very large databases. A reinvestigation of the concept of atom pairs initially reported by Carhart et al. and extended by Schneider et al. showed that a simple atom pair fingerprint (APfp) counting atom pairs at increasing topological distances in 2D-structures without atom property assignment correlates with various representations of molecular shape extracted from the 3D-structures. A related 55-dimensional atom pair fingerprint extended with atom properties (Xfp) provided an efficient pharmacophore fingerprint with good performance for ligand-based virtual screening such as the recovery of active compounds from decoys in DUD, and overlap with the ROCS 3D-pharmacophore scoring function. The APfp and Xfp data were organized for web-based extremely fast nearest-neighbor searching in ZINC (13.5 M compounds) and GDB-17 (50 M random subset) freely accessible at www.gdb.unibe.ch .
authors.affiliation: Department of Chemistry and Biochemistry, University of Berne , Freiestrasse 3, 3012 Berne Switzerland.
authors.forename: Mahendra
authors.initials: M
authors.lastname: Awale
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Reymond
mesh_terms: D062313:Databases, Pharmaceutical; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D048088:Informatics / Q000379:methods*; D008024:Ligands; D008968:Molecular Conformation; D014584:User-Computer Interface
chemical_list: D008024:Ligands