Accessing Transient Binding Pockets by Protein Engineering and Yeast Surface Display Screening.
Cell cytometry
Protein engineering
Transient binding pockets
Yeast surface display
Journal
Methods in molecular biology (Clifton, N.J.)
ISSN: 1940-6029
Titre abrégé: Methods Mol Biol
Pays: United States
ID NLM: 9214969
Informations de publication
Date de publication:
2023
2023
Historique:
medline:
7
7
2023
pubmed:
5
7
2023
entrez:
5
7
2023
Statut:
ppublish
Résumé
The binding pocket of some therapeutic targets can acquire multiple conformations that, to some extent, depend on the protein dynamics and the interaction with other molecules. The inability to reach the binding pocket can impose a substantial or even insurmountable barrier for the de novo identification or optimization of small-molecule ligands. Herein, we describe a protocol for the engineering of a target protein and a yeast display FACS sorting strategy to identify protein variants with a stable transient binding pocket with improved binding for a cryptic site-specific ligand. This strategy may facilitate drug discovery using the resulting protein variants with accessible binding pockets for ligand screening.
Identifiants
pubmed: 37405652
doi: 10.1007/978-1-0716-3279-6_14
doi:
Substances chimiques
Ligands
0
Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
249-274Informations de copyright
© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Laurie ATR, Jackson RM (2006) Methods for the prediction of protein-ligand binding sites for structure-based drug design and virtual ligand screening. Curr Protein Pept Sci 7:395–406
doi: 10.2174/138920306778559386
pubmed: 17073692
Gao M, Skolnick J (2013) A comprehensive survey of small-molecule binding pockets in proteins. PLoS Comput Biol 9:e1003302
doi: 10.1371/journal.pcbi.1003302
pubmed: 24204237
pmcid: 3812058
Kokh DB, Czodrowski P, Rippmann F, Wade RC (2016) Perturbation approaches for exploring protein binding site flexibility to predict transient binding pockets. J Chem Theory Comput 12:4100–4113
doi: 10.1021/acs.jctc.6b00101
pubmed: 27399277
Stank A, Kokh DB, Fuller JC, Wade RC (2016) Protein binding pocket dynamics. Acc Chem Res 49:809–815
doi: 10.1021/acs.accounts.5b00516
pubmed: 27110726
Beglov D, Hall DR, Wakefield AE, Luo L, Allen KN, Kozakov D, Whitty A, Vajda S (2018) Exploring the structural origins of cryptic sites on proteins. Proc Natl Acad Sci 115:E3416–E3425
doi: 10.1073/pnas.1711490115
pubmed: 29581267
pmcid: 5899430
Durrant JD, McCammon JA (2011) Molecular dynamics simulations and drug discovery. BMC Biol 9:71
doi: 10.1186/1741-7007-9-71
pubmed: 22035460
pmcid: 3203851
Shan Y, Mysore VP, Leffler AE, Kim ET, Sagawa S, Shaw DE (2022) How does a small molecule bind at a cryptic binding site? PLoS Comput Biol 18:e1009817
doi: 10.1371/journal.pcbi.1009817
pubmed: 35239648
pmcid: 8893328
Arkin MR, Randal M, DeLano WL et al (2003) Binding of small molecules to an adaptive protein–protein interface. Proc Natl Acad Sci 100:1603–1608
doi: 10.1073/pnas.252756299
pubmed: 12582206
pmcid: 149879
Bowman GR, Geissler PL (2012) Equilibrium fluctuations of a single folded protein reveal a multitude of potential cryptic allosteric sites. PNAS. https://doi.org/10.1073/pnas.1209309109/-/DCSupplemental
Huggins DJ, Sherman W, Tidor B (2012) Rational approaches to improving selectivity in drug design. J Med Chem 55:1424–1444
doi: 10.1021/jm2010332
pubmed: 22239221
pmcid: 3285144
Umezawa K, Kii I (2021) Druggable Transient Pockets in Protein Kinases. Molecules 26:651
doi: 10.3390/molecules26030651
pubmed: 33513739
pmcid: 7865889
Nussinov R, Ma B (2012) Protein dynamics and conformational selection in bidirectional signal transduction. BMC Biol 10:2
doi: 10.1186/1741-7007-10-2
pubmed: 22277130
pmcid: 3266202
Eyrisch S, Helms V (2007) Transient pockets on protein surfaces involved in protein−protein interaction. J Med Chem 50:3457–3464
doi: 10.1021/jm070095g
pubmed: 17602601
Kokh DB, Richter S, Henrich S, Czodrowski P, Rippmann F, Wade RC (2013) TRAPP: a tool for analysis of Transient binding Pockets in Proteins. J Chem Inf Model 53:1235–1252
doi: 10.1021/ci4000294
pubmed: 23621586
Meiler J, Baker D (2006) ROSETTALIGAND: protein-small molecule docking with full side-chain flexibility. Proteins: Structure Function Bioinformatics 65:538–548
doi: 10.1002/prot.21086
Zacharias M (2004) Rapid protein-ligand docking using soft modes from molecular dynamics simulations to account for protein deformability: binding of FK506 to FKBP. Proteins: Structure, Function Bioinformatics 54:759–767
doi: 10.1002/prot.10637
Oleinikovas V, Saladino G, Cossins BP, Gervasio FL (2016) Understanding cryptic pocket formation in protein targets by enhanced sampling simulations. J Am Chem Soc 138:14257–14263
doi: 10.1021/jacs.6b05425
pubmed: 27726386
Kumar S, Ma B, Tsai C-J, Wolfson H, Nussinov R (1999) Folding funnels and conformational transitions via hinge-bending motions. Cell Biochem Biophys 31:141–164
doi: 10.1007/BF02738169
pubmed: 10593256
Ma B, Kumar S, Tsai C-J, Nussinov R (1999) Folding funnels and binding mechanisms. Protein Eng Des Sel 12:713–720
doi: 10.1093/protein/12.9.713
Teague SJ (2003) Implications of protein flexibility for drug discovery. Nat Rev Drug Discov 2:527–541
doi: 10.1038/nrd1129
pubmed: 12838268
Rath VL, Ammirati M, Danley DE et al (2000) Human liver glycogen phosphorylase inhibitors bind at a new allosteric site. Chem Biol 7:677–682
doi: 10.1016/S1074-5521(00)00004-1
pubmed: 10980448
Maun HR, Eigenbrot C, Lazarus RA (2003) Engineering exosite peptides for complete inhibition of factor VIIa using a protease switch with substrate phage. J Biol Chem 278:21823–21830
doi: 10.1074/jbc.M300951200
pubmed: 12657647
Hardy JA, Lam J, Nguyen JT, O’Brien T, Wells JA (2004) Discovery of an allosteric site in the caspases. Proc Natl Acad Sci 101:12461–12466
doi: 10.1073/pnas.0404781101
pubmed: 15314233
pmcid: 514654
Braisted AC, Oslob JD, Delano WL, Hyde J, McDowell RS, Waal N, Yu C, Arkin MR, Raimundo BC (2003) Discovery of a potent small molecule IL-2 inhibitor through fragment assembly. J Am Chem Soc 125:3714–3715
doi: 10.1021/ja034247i
pubmed: 12656598
Gaali S, Kirschner A, Cuboni S et al (2015) Selective inhibitors of the FK506-binding protein 51 by induced fit. Nat Chem Biol 11:33–37
doi: 10.1038/nchembio.1699
pubmed: 25436518
Lerma Romero JA, Meyners C, Christmann A, Reinbold LM, Charalampidou A, Hausch F, Kolmar H (2022) Binding pocket stabilization by high-throughput screening of yeast display libraries. Front Mol Biosci. https://doi.org/10.3389/fmolb.2022.1023131
Benatuil L, Perez JM, Belk J, Hsieh CM (2010) An improved yeast transformation method for the generation of very large human antibody libraries. Protein Eng Des Sel 23:155–159
doi: 10.1093/protein/gzq002
pubmed: 20130105
Bogen JP, Grzeschik J, Krah S, Zielonka S, Kolmar H (2020) Rapid generation of chicken immune libraries for yeast surface display. Methods Mol Biol 2070:289–302
Becker S, Schmoldt HU, Adams TM, Wilhelm S, Kolmar H (2004) Ultra-high-throughput screening based on cell-surface display and fluorescence-activated cell sorting for the identification of novel biocatalysts. Curr Opin Biotechnol 15:323–329
doi: 10.1016/j.copbio.2004.06.001
pubmed: 15296929
Benatuil L, Perez JM, Belk J, Hsieh C-M (2010) An improved yeast transformation method for the generation of very large human antibody libraries. Protein Eng Des Sel 23:155–159
doi: 10.1093/protein/gzq002
pubmed: 20130105