Recent Advances in Structure-based Virtual Screening of G-protein Coupled Receptors

Overview

Journal AAPS J

Specialty Pharmacology

Date 2009 Mar 18

PMID 19291412

Citations 5

Authors

Subramaniam Ananthan

Wei Zhang

Judith Varady Hobrath

Affiliations

Soon will be listed here.

Abstract

In addition to the rhodopsin crystal structure, high-resolution crystal structures of ligand-mediated G-protein-coupled receptors (GPCRs) have recently become available, and these have become attractive templates for developing homology models of several GPCRs of therapeutic interest. These crystal structures and the homology models derived from them have provided significant insights into ligand-receptor interactions. Moreover, several studies have demonstrated that the structural models are indeed suitable for virtual screening of compound databases to identify new ligands for various GPCRs. Recent examples of such virtual screening against GPCRs are discussed in this review.

Citing Articles

ImmtorLig_DB: repertoire of virtually screened small molecules against immune receptors to bolster host immunity.

Chatterjee D, Kaur G, Muradia S, Singh B, Agrewala J Sci Rep. 2019; 9(1):3092.

PMID: 30816123 PMC: 6395627. DOI: 10.1038/s41598-018-36179-5.

Recent Advances and Applications of Molecular Docking to G Protein-Coupled Receptors.

Bartuzi D, Kaczor A, Targowska-Duda K, Matosiuk D Molecules. 2017; 22(2).

PMID: 28241450 PMC: 6155844. DOI: 10.3390/molecules22020340.

Monte Carlo loop refinement and virtual screening of the thyroid-stimulating hormone receptor transmembrane domain.

Ali M, Latif R, Davies T, Mezei M J Biomol Struct Dyn. 2014; 33(5):1140-52.

PMID: 25012978 PMC: 4484770. DOI: 10.1080/07391102.2014.932310.

How well do the substrates KISS the enzyme? Molecular docking program selection for feruloyl esterases.

Udatha D, Sugaya N, Olsson L, Panagiotou G Sci Rep. 2012; 2:323.

PMID: 22435086 PMC: 3308130. DOI: 10.1038/srep00323.

Using ligand-based virtual screening to allosterically stabilize the activated state of a GPCR.

Taylor C, Rockweiler N, Liu C, Rikimaru L, Tunemalm A, Kisselev O Chem Biol Drug Des. 2010; 75(3):325-32.

PMID: 20659113 PMC: 2911999. DOI: 10.1111/j.1747-0285.2009.00944.x.

References

Cavasotto C, Orry A, Murgolo N, Czarniecki M, Kocsi S, Hawes B . Discovery of novel chemotypes to a G-protein-coupled receptor through ligand-steered homology modeling and structure-based virtual screening. J Med Chem. 2008; 51(3):581-8. DOI: 10.1021/jm070759m. View

Taylor C, Barda Y, Kisselev O, Marshall G . Modulating G-protein coupled receptor/G-protein signal transduction by small molecules suggested by virtual screening. J Med Chem. 2008; 51(17):5297-303. PMC: 2664537. DOI: 10.1021/jm800326q. View

Evers A, Hessler G, Matter H, Klabunde T . Virtual screening of biogenic amine-binding G-protein coupled receptors: comparative evaluation of protein- and ligand-based virtual screening protocols. J Med Chem. 2005; 48(17):5448-65. DOI: 10.1021/jm050090o. View

Rasmussen S, Choi H, Rosenbaum D, Kobilka T, Thian F, Edwards P . Crystal structure of the human beta2 adrenergic G-protein-coupled receptor. Nature. 2007; 450(7168):383-7. DOI: 10.1038/nature06325. View

Ghosh S, Nie A, An J, Huang Z . Structure-based virtual screening of chemical libraries for drug discovery. Curr Opin Chem Biol. 2006; 10(3):194-202. DOI: 10.1016/j.cbpa.2006.04.002. View

Cherezov V, Rosenbaum D, Hanson M, Rasmussen S, Thian F, Kobilka T . High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor. Science. 2007; 318(5854):1258-65. PMC: 2583103. DOI: 10.1126/science.1150577. View

Hanson M, Cherezov V, Griffith M, Roth C, Jaakola V, Chien E . A specific cholesterol binding site is established by the 2.8 A structure of the human beta2-adrenergic receptor. Structure. 2008; 16(6):897-905. PMC: 2601552. DOI: 10.1016/j.str.2008.05.001. View

Singh N, Cheve G, Ferguson D, McCurdy C . A combined ligand-based and target-based drug design approach for G-protein coupled receptors: application to salvinorin A, a selective kappa opioid receptor agonist. J Comput Aided Mol Des. 2006; 20(7-8):471-93. DOI: 10.1007/s10822-006-9067-x. View

Warne T, Serrano-Vega M, Baker J, Moukhametzianov R, Edwards P, Henderson R . Structure of a beta1-adrenergic G-protein-coupled receptor. Nature. 2008; 454(7203):486-91. PMC: 2923055. DOI: 10.1038/nature07101. View

10.

Radestock S, Weil T, Renner S . Homology model-based virtual screening for GPCR ligands using docking and target-biased scoring. J Chem Inf Model. 2008; 48(5):1104-17. DOI: 10.1021/ci8000265. View

11.

Chen J, Wang J, Xie X . GPCR structure-based virtual screening approach for CB2 antagonist search. J Chem Inf Model. 2007; 47(4):1626-37. DOI: 10.1021/ci7000814. View

12.

Kiss R, Kiss B, Konczol A, Szalai F, Jelinek I, Laszlo V . Discovery of novel human histamine H4 receptor ligands by large-scale structure-based virtual screening. J Med Chem. 2008; 51(11):3145-53. DOI: 10.1021/jm7014777. View

13.

Topiol S, Sabio M . Use of the X-ray structure of the Beta2-adrenergic receptor for drug discovery. Bioorg Med Chem Lett. 2008; 18(5):1598-602. DOI: 10.1016/j.bmcl.2008.01.063. View

14.

Klebe G . Virtual ligand screening: strategies, perspectives and limitations. Drug Discov Today. 2006; 11(13-14):580-94. PMC: 7108249. DOI: 10.1016/j.drudis.2006.05.012. View

15.

Scheerer P, Park J, Hildebrand P, Kim Y, Krauss N, Choe H . Crystal structure of opsin in its G-protein-interacting conformation. Nature. 2008; 455(7212):497-502. DOI: 10.1038/nature07330. View

16.

de Graaf C, Rognan D . Selective structure-based virtual screening for full and partial agonists of the beta2 adrenergic receptor. J Med Chem. 2008; 51(16):4978-85. DOI: 10.1021/jm800710x. View

17.

Park J, Scheerer P, Hofmann K, Choe H, Ernst O . Crystal structure of the ligand-free G-protein-coupled receptor opsin. Nature. 2008; 454(7201):183-7. DOI: 10.1038/nature07063. View

18.

Engel S, Skoumbourdis A, Childress J, Neumann S, Deschamps J, Thomas C . A virtual screen for diverse ligands: discovery of selective G protein-coupled receptor antagonists. J Am Chem Soc. 2008; 130(15):5115-23. DOI: 10.1021/ja077620l. View

19.

Kiss R, Noszal B, Racz A, Falus A, Eros D, Keseru G . Binding mode analysis and enrichment studies on homology models of the human histamine H4 receptor. Eur J Med Chem. 2007; 43(5):1059-70. DOI: 10.1016/j.ejmech.2007.07.014. View

20.

Teller D, Okada T, Behnke C, Palczewski K, Stenkamp R . Advances in determination of a high-resolution three-dimensional structure of rhodopsin, a model of G-protein-coupled receptors (GPCRs). Biochemistry. 2001; 40(26):7761-72. PMC: 1698954. DOI: 10.1021/bi0155091. View