scholarly journals Protein Flexibility and Ligand Rigidity: A Thermodynamic and Kinetic Study of ITAM-Based Ligand Binding to Syk Tandem SH2

ChemBioChem ◽  
2005 ◽  
Vol 6 (12) ◽  
pp. 2261-2270 ◽  
Author(s):  
Nico J. de Mol ◽  
M. Isabel Catalina ◽  
Frank J. Dekker ◽  
Marcel J. E. Fischer ◽  
Albert J. R. Heck ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Kinetic Study ◽  
Protein Flexibility

scholarly journals The role of water and protein flexibility in the structure-based virtual screening of allosteric GPCR modulators: an mGlu5 receptor case study

2019 ◽  
Vol 33 (9) ◽  
pp. 787-797 ◽  
Author(s):  
Zoltán Orgován ◽  
György G. Ferenczy ◽  
György M. Keserű
Keyword(s):  
Virtual Screening ◽  
Ligand Binding ◽  
Conformational Changes ◽  
Metabotropic Glutamate Receptor ◽  
Protein Structures ◽  
Protein Flexibility ◽  
Water Molecules ◽  
Large Set ◽  
Allosteric Modulators

Abstract Stabilizing unique receptor conformations, allosteric modulators of G-protein coupled receptors (GPCRs) might open novel treatment options due to their new pharmacological action, their enhanced specificity and selectivity in both binding and signaling. Ligand binding occurs at intrahelical allosteric sites and involves significant induced fit effects that include conformational changes in the local protein environment and water networks. Based on the analysis of available crystal structures of metabotropic glutamate receptor 5 (mGlu5) we investigated these effects in the binding of mGlu5 receptor negative allosteric modulators. A large set of retrospective virtual screens revealed that the use of multiple protein structures and the inclusion of selected water molecules improves virtual screening performance compared to conventional docking strategies. The role of water molecules and protein flexibility in ligand binding can be taken into account efficiently by the proposed docking protocol that provided reasonable enrichment of true positives. This protocol is expected to be useful also for identifying intrahelical allosteric modulators for other GPCR targets.

scholarly journals Protein stability induced by ligand binding correlates with changes in protein flexibility

2003 ◽  
Vol 12 (7) ◽  
pp. 1496-1506 ◽  
Author(s):  
María Soledad Celej ◽  
Guillermo G. Montich ◽  
Gerardo D. Fidelio
Keyword(s):  
Ligand Binding ◽  
Protein Stability ◽  
Protein Flexibility

scholarly journals GPCRs through the keyhole: the role of protein flexibility in ligand binding to β-adrenoceptors

2016 ◽  
Vol 35 (12) ◽  
pp. 2604-2619 ◽  
Author(s):  
Abigail L. Emtage ◽  
Shailesh N. Mistry ◽  
Peter M. Fischer ◽  
Barrie Kellam ◽  
Charles A. Laughton
Keyword(s):  
Ligand Binding ◽  
Protein Flexibility

scholarly journals Protein Flexibility Reduces Solvent-Mediated Friction Barriers of Ligand Binding to a Hydrophobic Surface Patch

2021 ◽  
Author(s):  
Christopher Päslack ◽  
Lars V Schäfer ◽  
Matthias Heyden
Keyword(s):  
Ligand Binding ◽  
Protein Flexibility ◽  
Hydrophobic Surface ◽  
Model Systems ◽  
Surface Patch ◽  
Protein Motions ◽  
Internal Protein

Solvent fluctuations have been explored in detail for idealized and rigid hydrophobic model systems, but so far it has remained unclear how internal protein motions and their coupling to the...

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