title: e-LEA3D: a computational-aided drug design web server.
abstract: e-LEA3D web server integrates three complementary tools to perform computer-aided drug design based on molecular fragments. In drug discovery projects, there is a considerable interest in identifying novel and diverse molecular scaffolds to enhance chances of success. The de novo drug design tool is used to invent new ligands to optimize a user-specified scoring function. The composite scoring function includes both structure- and ligand-based evaluations. The de novo approach is an alternative to a blind virtual screening of large compound collections. A heuristic based on a genetic algorithm rapidly finds which fragments or combination of fragments fit a QSAR model or the binding site of a protein. While the approach is ideally suited for scaffold-hopping, this module also allows a scan for possible substituents to a user-specified scaffold. The second tool offers a traditional virtual screening and filtering of an uploaded library of compounds. The third module addresses the combinatorial library design that is based on a user-drawn scaffold and reactants coming, for example, from a chemical supplier. The e-LEA3D server is available at: http://bioinfo.ipmc.cnrs.fr/lea.html.
authors.affiliation: CNRS UMR6097-Université Nice-Sophia Antipolis 660, route des lucioles 06560 Valbonne, France. douguet@ipmc.cnrs.fr
authors.forename: Dominique
authors.initials: D
authors.lastname: Douguet
mesh_terms: D019817:Benzoic Acid / Q000737:chemistry; D019295:Computational Biology; D015195:Drug Design; D020407:Internet; D008024:Ligands; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D018168:Receptors, Retinoic Acid / Q000737:chemistry; D000072482:Retinoic Acid Receptor alpha; D012984:Software; D014584:User-Computer Interface
chemical_list: D008024:Ligands; D004364:Pharmaceutical Preparations; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D019817:Benzoic Acid
references.citation: J Comput Aided Mol Des. 1995 Feb;9(1):13-32
references.pmid: 7751867
references.citation: Med Res Rev. 2003 Sep;23(5):606-32
references.pmid: 12789688
references.citation: J Chem Inf Model. 2009 Oct;49(10):2211-20
references.pmid: 19788263
references.citation: Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W665-7
references.pmid: 15215472
references.citation: Drug Discov Today. 2008 Aug;13(15-16):659-64
references.pmid: 18675760
references.citation: J Mol Biol. 1996 Aug 23;261(3):470-89
references.pmid: 8780787
references.citation: J Chem Inf Model. 2005 Jan-Feb;45(1):177-82
references.pmid: 15667143
references.citation: J Am Chem Soc. 2009 Jul 1;131(25):8732-3
references.pmid: 19505099
references.citation: Nature. 2004 Dec 16;432(7019):855-61
references.pmid: 15602551
references.citation: Biochem Pharmacol. 2009 Aug 1;78(3):217-23
references.pmid: 19481639
references.citation: Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W219-24
references.pmid: 16844997
references.citation: Nucleic Acids Res. 2009 Jul;37(Web Server issue):W504-9
references.pmid: 19429687
references.citation: J Mol Graph Model. 2000 Aug-Oct;18(4-5):358-67, 526
references.pmid: 11143555
references.citation: J Chem Inf Model. 2009 Jan;49(1):84-96
references.pmid: 19125657
references.citation: Nucleic Acids Res. 2008 Jul 1;36(Web Server issue):W223-8
references.pmid: 18424800
references.citation: J Comput Aided Mol Des. 2002 Jul;16(7):459-78
references.pmid: 12510880
references.citation: Trends Biotechnol. 2009 Sep;27(9):512-21
references.pmid: 19679363
references.citation: Chem Biol Drug Des. 2008 Jul;72(1):16-26
references.pmid: 18564216
references.citation: Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W738-44
references.pmid: 16845110
references.citation: Drug Discov Today. 2008 Aug;13(15-16):665-9
references.pmid: 18675761
references.citation: J Med Chem. 2002 Jan 3;45(1):137-42
references.pmid: 11754585
references.citation: J Chem Inf Comput Sci. 1987 Feb;27(1):21-35
references.pmid: 3558506
references.citation: J Med Chem. 1993 Nov 26;36(24):3863-70
references.pmid: 8254618
references.citation: Curr Protein Pept Sci. 2007 Aug;8(4):381-411
references.pmid: 17696871
references.citation: J Am Chem Soc. 2004 Oct 13;126(40):12809-18
references.pmid: 15469276
references.citation: Mol Divers. 2009 May;13(2):241-5
references.pmid: 19255865
references.citation: Angew Chem Int Ed Engl. 2004 Dec 17;44(1):116-20
references.pmid: 15599912
references.citation: J Comput Aided Mol Des. 1995 Apr;9(2):181-202
references.pmid: 7608749
references.citation: J Chem Inf Model. 2008 Feb;48(2):256-61
references.pmid: 18254609
references.citation: Proc Natl Acad Sci U S A. 2004 Feb 10;101(6):1449-54
references.pmid: 14757816
references.citation: Nucleic Acids Res. 2007 Jul;35(Web Server issue):W568-72
references.pmid: 17485475
references.citation: Nucleic Acids Res. 2008 Jul 1;36(Web Server issue):W47-54
references.pmid: 18492720
references.citation: J Med Chem. 2009 Sep 24;52(18):5712-20
references.pmid: 19719084
references.citation: J Comput Aided Mol Des. 2001 Oct;15(10):911-33
references.pmid: 11918076
references.citation: J Med Chem. 2005 Apr 7;48(7):2457-68
references.pmid: 15801836
references.citation: J Comput Aided Mol Des. 2002 Jan;16(1):11-26
references.pmid: 12197663