title: Frog2: Efficient 3D conformation ensemble generator for small compounds.
abstract: Frog is a web tool dedicated to small compound 3D generation. Here we present the new version, Frog2, which allows the generation of conformation ensembles of small molecules starting from either 1D, 2D or 3D description of the compounds. From a compound description in one of the SMILES, SDF or mol2 formats, the server will return an ensemble of diverse conformers generated using a two stage Monte Carlo approach in the dihedral space. When starting from 1D or 2D description of compounds, Frog2 is capable to detect the sites of ambiguous stereoisomery, and thus to sample different stereoisomers. Frog2 also embeds new energy minimization and ring generation facilities that solve the problem of some missing cycle structures in the Frog1 ring library. Finally, the optimized generator of conformation ensembles in Frog2 results in a gain of computational time permitting Frog2 to be up to 20 times faster that Frog1, while producing satisfactory conformations in terms of structural quality and conformational diversity. The high speed and the good quality of generated conformational ensembles makes it possible the treatment of larger compound collections using Frog2. The server and documentation are freely available at http://bioserv.rpbs.univ-paris-diderot.fr/Frog2.
authors.affiliation: MTi, INSERM UMR-S973, Université Paris Diderot-Paris 7, Bat. Lamarck case 7113, 35 rue H. Brion, F75205, Paris, France.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Miteva
authors.forename: Frederic
authors.initials: F
authors.lastname: Guyon
authors.forename: Pierre
authors.initials: P
authors.lastname: Tufféry
mesh_terms: D020407:Internet; D008958:Models, Molecular; D008968:Molecular Conformation; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012984:Software; D013237:Stereoisomerism
chemical_list: D004364:Pharmaceutical Preparations
references.citation: Eur J Med Chem. 2009 Apr;44(4):1405-9
references.pmid: 19022539
references.citation: J Chem Inf Model. 2008 Jan;48(1):1-24
references.pmid: 18183967
references.citation: Nucleic Acids Res. 2007 Jan;35(Database issue):D5-12
references.pmid: 17170002
references.citation: BMC Bioinformatics. 2008 Apr 10;9:184
references.pmid: 18402678
references.citation: Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W738-44
references.pmid: 16845110
references.citation: Curr Protein Pept Sci. 2007 Aug;8(4):381-411
references.pmid: 17696871
references.citation: Nature. 2004 Dec 16;432(7019):862-5
references.pmid: 15602552
references.citation: BMC Bioinformatics. 2008 Oct 16;9:438
references.pmid: 18925937
references.citation: J Chem Inf Model. 2006 May-Jun;46(3):991-8
references.pmid: 16711717
references.citation: J Med Chem. 2007 Feb 22;50(4):726-41
references.pmid: 17300160
references.citation: BMC Chem Biol. 2009 Nov 13;9:6
references.pmid: 19912625
references.citation: Science. 1992 Aug 21;257(5073):1078-82
references.pmid: 1509259
references.citation: Nucleic Acids Res. 2007 Jul;35(Web Server issue):W568-72
references.pmid: 17485475
references.citation: Expert Opin Drug Discov. 2008 Aug;3(8):841-51
references.pmid: 23484962
references.citation: Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19256-61
references.pmid: 18042718
references.citation: J Chem Inf Model. 2007 Nov-Dec;47(6):2462-74
references.pmid: 17892278
references.citation: J Chem Inf Model. 2009 Jan;49(1):108-19
references.pmid: 19123924
references.citation: Drug Discov Today. 2009 Jun;14(11-12):562-9
references.pmid: 19508918
references.citation: J Chem Inf Model. 2005 Jan-Feb;45(1):177-82
references.pmid: 15667143
references.citation: J Med Chem. 2004 Jun 3;47(12):2977-80
references.pmid: 15163179
references.citation: J Chem Inf Model. 2006 Jul-Aug;46(4):1848-61
references.pmid: 16859316
references.citation: J Chem Inf Model. 2005 May-Jun;45(3):673-84
references.pmid: 15921457
references.citation: ChemMedChem. 2009 Nov;4(11):1883-96
references.pmid: 19768722