Insight into the binding mode of HIF-2 agonists through molecular dynamic simulations and biological validation

2020 ◽  
pp. 112999
Author(s):  
Yancheng Yu ◽  
Quanwei Yu ◽  
Simeng Liu ◽  
Chenyang Wu ◽  
Xiaojin Zhang
Keyword(s):  
Molecular Dynamic ◽  
Binding Mode ◽  
Molecular Dynamic Simulations ◽  
Dynamic Simulations ◽  
Biological Validation ◽  
Insight Into

scholarly journals Exploring aromatic cage flexibility of the histone methyllysine reader protein Spindlin1 and its impact on binding mode prediction: an in silico study

2021 ◽  
Author(s):  
Chiara Luise ◽  
Dina Robaa ◽  
Wolfgang Sippl
Keyword(s):  
Molecular Dynamic ◽  
In Silico ◽  
Binding Pocket ◽  
Binding Mode ◽  
Molecular Dynamic Simulations ◽  
Flexible Docking ◽  
Dynamic Simulations ◽  
Binding Mode Prediction ◽  
Aromatic Cage ◽  
The Right

AbstractSome of the main challenges faced in drug discovery are pocket flexibility and binding mode prediction. In this work, we explored the aromatic cage flexibility of the histone methyllysine reader protein Spindlin1 and its impact on binding mode prediction by means of in silico approaches. We first investigated the Spindlin1 aromatic cage plasticity by analyzing the available crystal structures and through molecular dynamic simulations. Then we assessed the ability of rigid docking and flexible docking to rightly reproduce the binding mode of a known ligand into Spindlin1, as an example of a reader protein displaying flexibility in the binding pocket. The ability of induced fit docking was further probed to test if the right ligand binding mode could be obtained through flexible docking regardless of the initial protein conformation. Finally, the stability of generated docking poses was verified by molecular dynamic simulations. Accurate binding mode prediction was obtained showing that the herein reported approach is a highly promising combination of in silico methods able to rightly predict the binding mode of small molecule ligands in flexible binding pockets, such as those observed in some reader proteins.

Molecular dynamic simulations of the tubulin–human gamma synuclein complex: structural insight into the regulatory mechanism involved in inducing resistance against Taxol

2013 ◽  
Vol 9 (6) ◽  
pp. 1470 ◽  
Author(s):  
Manivel Panneerselvam ◽  
Kannan Muthu ◽  
Muthukumaran Jayaraman ◽  
Upasana Sridharan ◽  
Pranitha Jenardhanan ◽  
...  
Keyword(s):  
Molecular Dynamic ◽  
Regulatory Mechanism ◽  
Molecular Dynamic Simulations ◽  
Dynamic Simulations ◽  
Structural Insight ◽  
Complex Structural ◽  
Insight Into ◽  
Inducing Resistance

scholarly journals Discovery of Homobivalent Bitopic Ligands Of The Cannabinoid Cb2 Receptor

2020 ◽  
Author(s):  
Paula Morales ◽  
Gemma Navarro ◽  
Marc Gómez-Autet ◽  
Laura Redondo ◽  
Javier Fernandez-Ruiz ◽  
...  
Keyword(s):  
Molecular Dynamic ◽  
Binding Sites ◽  
Binding Mode ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Cb1 Receptors ◽  
Molecular Dynamic Simulations ◽  
Cb2 Receptor ◽  
Dynamic Simulations ◽  
Single Chemical

<p>Single chemical entities with potential to simultaneously interact with two binding sites are emerging strategies in medicinal chemistry. We have designed, synthesized and functionally characterized the first bitopic ligands for the CB2 receptor. These compounds selectively target CB2 versus CB1 receptors. Their binding mode was studied by molecular dynamic simulations and site-directed mutagenesis</p> <p><br></p>

scholarly journals Discovery of Homobivalent Bitopic Ligands Of The Cannabinoid Cb2 Receptor

2020 ◽  
Author(s):  
Paula Morales ◽  
Gemma Navarro ◽  
Marc Gómez-Autet ◽  
Laura Redondo ◽  
Javier Fernandez-Ruiz ◽  
...  
Keyword(s):  
Molecular Dynamic ◽  
Binding Sites ◽  
Binding Mode ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Cb1 Receptors ◽  
Molecular Dynamic Simulations ◽  
Cb2 Receptor ◽  
Dynamic Simulations ◽  
Single Chemical

<p>Single chemical entities with potential to simultaneously interact with two binding sites are emerging strategies in medicinal chemistry. We have designed, synthesized and functionally characterized the first bitopic ligands for the CB2 receptor. These compounds selectively target CB2 versus CB1 receptors. Their binding mode was studied by molecular dynamic simulations and site-directed mutagenesis</p> <p><br></p>

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