Binding site matching in rational drug design: algorithms and applications

Briefings in Bioinformatics
Misagh NaderiMichal Brylinski

Abstract

Interactions between proteins and small molecules are critical for biological functions. These interactions often occur in small cavities within protein structures, known as ligand-binding pockets. Understanding the physicochemical qualities of binding pockets is essential to improve not only our basic knowledge of biological systems, but also drug development procedures. In order to quantify similarities among pockets in terms of their geometries and chemical properties, either bound ligands can be compared to one another or binding sites can be matched directly. Both perspectives routinely take advantage of computational methods including various techniques to represent and compare small molecules as well as local protein structures. In this review, we survey 12 tools widely used to match pockets. These methods are divided into five categories based on the algorithm implemented to construct binding-site alignments. In addition to the comprehensive analysis of their algorithms, test sets and the performance of each method are described. We also discuss general pharmacological applications of computational pocket matching in drug repurposing, polypharmacology and side effects. Reflecting on the importance of these techniques in...Continue Reading

References

Nov 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·S Henikoff, J G Henikoff
Oct 1, 1980·Molecular and Cellular Endocrinology·J L Borgna, H Rochefort
Jan 9, 1996·Proceedings of the National Academy of Sciences of the United States of America·S Jones, J M Thornton
Jan 1, 1996·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·I KochE Wanke
Nov 29, 1996·Science·S B ShukerS W Fesik
Jan 1, 1997·Nucleic Acids Research·T J HubbardC Chothia
Sep 1, 1997·Nucleic Acids Research·S F AltschulD J Lipman
Aug 15, 1998·Journal of Molecular Graphics & Modelling·M HendlichG Barnickel
Oct 7, 1998·Protein Science : a Publication of the Protein Society·J LiangC Woodward
Oct 31, 1998·Protein Engineering·I N Shindyalov, P E Bourne
Dec 11, 1999·Nucleic Acids Research·S E BrennerM Levitt
Dec 11, 1999·Nucleic Acids Research·A Bairoch
May 18, 2000·Journal of Computer-aided Molecular Design·G P Brady, P F Stouten
Jul 12, 2001·Proceedings of the National Academy of Sciences of the United States of America·P CowardJ M Lehmann
Jan 29, 2002·Combinatorial Chemistry & High Throughput Screening·X ChenM K Gilson
May 31, 2002·Acta Crystallographica. Section D, Biological Crystallography·Helen M BermanChristine Zardecki
Oct 17, 2002·Journal of Molecular Biology·Stefan SchmittGerhard Klebe
Jun 26, 2003·Nucleic Acids Research·T Andrew BinkowskiJie Liang
May 12, 2004·Nature Reviews. Drug Discovery·Michael Dickson, Jean Paul Gagnon
May 19, 2004·Journal of Molecular Biology·Alexandra Shulman-PelegHaim J Wolfson
Feb 11, 2005·Bioinformatics·Alasdair T R Laurie, Richard M Jackson
Dec 31, 2005·Nucleic Acids Research·David S WishartJennifer Woolsey
Mar 9, 2006·The Journal of Clinical Endocrinology and Metabolism·Yasemin SevalAydin Arici
Mar 28, 2006·Journal of Chemical Information and Modeling·Esther KellenbergerDidier Rognan
Apr 15, 2006·Science·Anthony Mittermaier, Lewis E Kay
Sep 26, 2006·BMC Structural Biology·Bingding Huang, Michael Schroeder
Sep 28, 2006·Proceedings of the National Academy of Sciences of the United States of America·Megan WhitnallDes R Richardson
Nov 1, 2006·Protein Science : a Publication of the Protein Society·Min-Yi Shen, Andrej Sali
Mar 6, 2007·Journal of Molecular Biology·Abdullah KahramanJanet M Thornton
Mar 29, 2007·Journal of Chemical Information and Modeling·Janez Konc, Dusanka Janezic
May 5, 2007·Nucleic Acids Research·Sitao Wu, Yang Zhang
Jun 26, 2007·Protein Science : a Publication of the Protein Society·Yinghao WuJianpeng Ma
Jan 1, 2008·Proceedings of the National Academy of Sciences of the United States of America·Michal Brylinski, Jeffrey Skolnick
Apr 4, 2008·Proceedings of the National Academy of Sciences of the United States of America·Lei Xie, Philip E Bourne
May 10, 2008·Nucleic Acids Research·Alexandra Shulman-PelegHaim J Wolfson
Jul 16, 2008·Science·Monica CampillosPeer Bork
Sep 10, 2008·Nature Biotechnology·Jordi MestresRicard V Solé
Sep 27, 2008·Bioinformatics·L HolmA Schenkel
Oct 14, 2008·Nature Chemical Biology·Beth ApselZachary A Knight

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Citations

Jul 13, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Natacha CerisierAnne-Claude Camproux
Mar 19, 2020·Briefings in Bioinformatics·Natesh SinghBruno O Villoutreix
May 27, 2020·Expert Opinion on Drug Discovery·Rajan ChaudhariShuxing Zhang
Feb 6, 2020·Journal of Chemical Information and Modeling·Martin Simonovsky, Joshua Meyers

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