Atom Pair 2D-Fingerprints Perceive 3D-Molecular Shape and Pharmacophores for Very Fast Virtual Screening of ZINC and GDB-17

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• 作者：Mahendra Awale ; Jean-Louis Reymond
• 刊名：Journal of Chemical Information and Modeling
• 出版年：2014
• 出版时间：July 28, 2014
• 年：2014
• 卷：54
• 期：7
• 页码：1892-1907
• 全文大小：1248K
• ISSN：1549-960X

文摘

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.