title: Optimal ligand descriptor for pocket recognition based on the Beta-shape.
abstract: Structure-based virtual screening is one of the most important and common computational methods for the identification of predicted hit at the beginning of drug discovery. Pocket recognition and definition is frequently a prerequisite of structure-based virtual screening, reducing the search space of the predicted protein-ligand complex. In this paper, we present an optimal ligand shape descriptor for a pocket recognition algorithm based on the beta-shape, which is a derivative structure of the Voronoi diagram of atoms. We investigate six candidates for a shape descriptor for a ligand using statistical analysis: the minimum enclosing sphere, three measures from the principal component analysis of atoms, the van der Waals volume, and the beta-shape volume. Among them, the van der Waals volume of a ligand is the optimal shape descriptor for pocket recognition and best tunes the pocket recognition algorithm based on the beta-shape for efficient virtual screening. The performance of the proposed algorithm is verified by a benchmark test.
authors.affiliation: Voronoi Diagram Research Center, Hanyang University, Seoul, Korea.
authors.forename: Jae-Kwan
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Voronoi Diagram Research Center, Hanyang University, Seoul, Korea.
authors.forename: Chung-In
authors.initials: CI
authors.lastname: Won
authors.affiliation: School of Mechanical Engineering, Hanyang University, Seoul, Korea.
authors.forename: Jehyun
authors.initials: J
authors.lastname: Cha
authors.affiliation: Department of Industrial Engineering, Hanyang University, Seoul, Korea.
authors.forename: Kichun
authors.initials: K
authors.lastname: Lee
authors.affiliation: Voronoi Diagram Research Center, Hanyang University, Seoul, Korea; School of Mechanical Engineering, Hanyang University, Seoul, Korea.
authors.forename: Deok-Soo
authors.initials: DS
authors.lastname: Kim
mesh_terms: D000086:Acetazolamide / Q000737:chemistry*; D000465:Algorithms; D019985:Benchmarking; D001665:Binding Sites; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000737:chemistry; D002256:Carbonic Anhydrases / Q000737:chemistry*; D055808:Drug Discovery; D057166:High-Throughput Screening Assays; D006801:Humans; D008024:Ligands; D025341:Principal Component Analysis; D011485:Protein Binding; D011487:Protein Conformation; D018167:Receptors, Calcitriol / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014584:User-Computer Interface
chemical_list: D008024:Ligands; D018167:Receptors, Calcitriol; C579457:VDR protein, human; C055085:calcipotriene; D002256:Carbonic Anhydrases; C477378:carbonic anhydrase XII; D002117:Calcitriol; D000086:Acetazolamide
references.citation: J Biol Chem. 2002 Nov 1;277(44):42233-40
references.pmid: 12140288
references.citation: J Biomol Struct Dyn. 2011 Aug;29(1):219-42
references.pmid: 21696235
references.citation: J Am Chem Soc. 2009 Jun 3;131(21):7390-401
references.pmid: 19432426
references.citation: J Mol Biol. 1996 Feb 16;256(1):201-13
references.pmid: 8609611
references.citation: J Chem Inf Model. 2010 Apr 26;50(4):589-603
references.pmid: 20205445
references.citation: J Comput Aided Mol Des. 2000 May;14(4):383-401
references.pmid: 10815774
references.citation: Curr Opin Chem Biol. 2004 Aug;8(4):365-70
references.pmid: 15288245
references.citation: J Comb Chem. 1999 Jan;1(1):55-68
references.pmid: 10746014
references.citation: Genet Epidemiol. 2007 May;31(4):306-15
references.pmid: 17323372
references.citation: Science. 2000 Sep 15;289(5486):1938-42
references.pmid: 10988075
references.citation: Epidemiol Perspect Innov. 2006 Oct 05;3:11
references.pmid: 17022816
references.citation: BMC Bioinformatics. 2008 May 16;9:238
references.pmid: 18485205
references.citation: Cancer. 1950 Jan;3(1):32-5
references.pmid: 15405679
references.citation: J Mol Model. 2003 Feb;9(1):47-57
references.pmid: 12638011
references.citation: Proteins. 2006 Jun 1;63(4):892-906
references.pmid: 16477622
references.citation: Curr Opin Pharmacol. 2004 Oct;4(5):490-6
references.pmid: 15351354
references.citation: J Mol Graph Model. 2011 Feb;29(5):773-6
references.pmid: 21147010
references.citation: J Mol Graph Model. 2008 Apr;26(7):1104-12
references.pmid: 18023220
references.citation: Proteins. 2002 Jun 1;47(4):409-43
references.pmid: 12001221
references.citation: Curr Opin Chem Biol. 2006 Jun;10(3):194-202
references.pmid: 16675286
references.citation: J Mol Graph Model. 2010 Nov;29(3):425-35
references.pmid: 20855222
references.citation: Mol Biotechnol. 2009 May;42(1):1-13
references.pmid: 19082769
references.citation: J Med Chem. 2007 Feb 22;50(4):726-41
references.pmid: 17300160
references.citation: Nucleic Acids Res. 2009 Jan;37(Database issue):D387-92
references.pmid: 18931379
references.citation: J Mol Graph Model. 2010 Jan;28(5):383-400
references.pmid: 19850503
references.citation: J Comput Chem. 2013 Nov 15;34(30):2647-56
references.pmid: 24108416
references.citation: J Mol Signal. 2008 Jan 02;3:1
references.pmid: 18171471
references.citation: Nucleic Acids Res. 2009 Jan;37(Database issue):D347-54
references.pmid: 18948282
references.citation: J Mol Graph. 1992 Dec;10(4):229-34
references.pmid: 1476996
references.citation: Nucleic Acids Res. 2006 Jan 1;34(Database issue):D306-9
references.pmid: 16381873
references.citation: Oncogene. 2003 Sep 18;22(40):6151-9
references.pmid: 13679853
references.citation: Curr Opin Struct Biol. 2003 Jun;13(3):389-95
references.pmid: 12831892
references.citation: Bioinformatics. 2010 Oct 15;26(20):2549-55
references.pmid: 20819959
references.citation: Science. 2004 Mar 19;303(5665):1813-8
references.pmid: 15031495
references.citation: Curr Opin Chem Biol. 2007 Oct;11(5):494-502
references.pmid: 17936059
references.citation: Bioorg Med Chem Lett. 2009 Oct 1;19(19):5769-72
references.pmid: 19706358
references.citation: Protein Sci. 1996 Dec;5(12):2438-52
references.pmid: 8976552
references.citation: J Comput Aided Mol Des. 1990 Dec;4(4):337-54
references.pmid: 2092080
references.citation: J Mol Biol. 1982 Oct 25;161(2):269-88
references.pmid: 7154081
references.citation: J Comput Chem. 2012 May 15;33(13):1252-73
references.pmid: 22396194
references.citation: J Mol Graph. 1989 Dec;7(4):243-5
references.pmid: 2486827
references.citation: Protein Sci. 1998 Sep;7(9):1884-97
references.pmid: 9761470
references.citation: Proteins. 2014 Sep;82(9):1829-49
references.pmid: 24677176