scholarly journals Dissecting the Influence of Protein Flexibility on the Location and Thermodynamic Profile of Explicit Water Molecules in Protein–Ligand Binding

2016 ◽  
Vol 12 (9) ◽  
pp. 4578-4592 ◽  
Author(s):  
Ying Yang ◽  
Markus A. Lill
Keyword(s):  
Ligand Binding ◽  
Protein Flexibility ◽  
Water Molecules ◽  
Explicit Water

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.

An efficient and robust procedure to calculate absorption spectra of aqueous charged species applied to NO2-

2021 ◽  
Author(s):  
Lina Uribe ◽  
Sara Gómez ◽  
Tommaso Giovannini ◽  
Franco Egidi ◽  
Albeiro Restrepo
Keyword(s):  
Potential Energy ◽  
Absorption Spectra ◽  
Potential Energy Surfaces ◽  
Quantum Potential ◽  
Water Molecules ◽  
Accurate Calculation ◽  
Charged Species ◽  
Energy Surfaces ◽  
Explicit Water

Accurate calculation of absorption spectra of aqueous NO2- requires rigorously sampling the quantum potential energy surfaces for microsolvation of NO2- with at least five explicit water molecules and embedding the...

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

Improving protein–ligand binding prediction by considering the bridging water molecules in Autodock

2019 ◽  
Vol 18 (05) ◽  
pp. 1950027 ◽  
Author(s):  
Qiangna Lu ◽  
Lian-Wen Qi ◽  
Jinfeng Liu
Keyword(s):  
Ligand Binding ◽  
Considerable Improvement ◽  
Ligand Docking ◽  
Water Molecules ◽  
Binding Modes ◽  
Binding Prediction ◽  
Docking Simulations ◽  
Protein Ligand Interactions ◽  
Ligand Interactions ◽  
Docking Program

Water plays a significant role in determining the protein–ligand binding modes, especially when water molecules are involved in mediating protein–ligand interactions, and these important water molecules are receiving more and more attention in recent years. Considering the effects of water molecules has gradually become a routine process for accurate description of the protein–ligand interactions. As a free docking program, Autodock has been most widely used in predicting the protein–ligand binding modes. However, whether the inclusion of water molecules in Autodock would improve its docking performance has not been systematically investigated. Here, we incorporate important bridging water molecules into Autodock program, and systematically investigate the effectiveness of these water molecules in protein–ligand docking. This approach was evaluated using 18 structurally diverse protein–ligand complexes, in which several water molecules bridge the protein–ligand interactions. Different treatment of water molecules were tested by using the fixed and rotatable water molecules, and a considerable improvement in successful docking simulations was found when including these water molecules. This study illustrates the necessity of inclusion of water molecules in Autodock docking, and emphasizes the importance of a proper treatment of water molecules in protein–ligand binding predictions.

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
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