Coulombic and Hydrophobic Interactions in the First Intracellular Loop Are Vital for Bradykinin B2 Receptor Ligand Binding and Consequent Signal Transduction†

Biochemistry ◽  
2005 ◽  
Vol 44 (14) ◽  
pp. 5295-5306 ◽  
Author(s):  
Jun Yu ◽  
Peter Polgar ◽  
David Lubinsky ◽  
Megna Gupta ◽  
Lei Wang ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Ligand Binding ◽  
Hydrophobic Interactions ◽  
Intracellular Loop ◽  
Receptor Ligand ◽  
Bradykinin B2 Receptor

Aspirin inhibits human bradykinin B2 receptor ligand binding function

2008 ◽  
Vol 75 (9) ◽  
pp. 1807-1816 ◽  
Author(s):  
Joëlle Gardes ◽  
Stéphanie Michineau ◽  
Anne Pizard ◽  
François Alhenc-Gelas ◽  
Rabary M. Rajerison
Keyword(s):  
Ligand Binding ◽  
Receptor Ligand ◽  
Bradykinin B2 Receptor ◽  
Binding Function

scholarly journals Cryptic-site binding mechanism of medium-sized Bcl-xL inhibiting compounds elucidated by McMD-based dynamic docking simulations

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gert-Jan Bekker ◽  
Ikuo Fukuda ◽  
Junichi Higo ◽  
Yoshifumi Fukunishi ◽  
Narutoshi Kamiya
Keyword(s):  
Ligand Binding ◽  
Cancer Progression ◽  
Hydrophobic Interactions ◽  
Binding Mechanism ◽  
Docking Simulations ◽  
Large Conformational Change ◽  
Binding Pockets ◽  
Dynamic Docking ◽  
Site Binding ◽  
Apo State

AbstractWe have performed multicanonical molecular dynamics (McMD) based dynamic docking simulations to study and compare the binding mechanism between two medium-sized inhibitors (ABT-737 and WEHI-539) that bind to the cryptic site of Bcl-xL, by exhaustively sampling the conformational and configurational space. Cryptic sites are binding pockets that are transiently formed in the apo state or are induced upon ligand binding. Bcl-xL, a pro-survival protein involved in cancer progression, is known to have a cryptic site, whereby the shape of the pocket depends on which ligand is bound to it. Starting from the apo-structure, we have performed two independent McMD-based dynamic docking simulations for each ligand, and were able to obtain near-native complex structures in both cases. In addition, we have also studied their interactions along their respective binding pathways by using path sampling simulations, which showed that the ligands form stable binding configurations via predominantly hydrophobic interactions. Although the protein started from the apo state, both ligands modulated the pocket in different ways, shifting the conformational preference of the sub-pockets of Bcl-xL. We demonstrate that McMD-based dynamic docking is a powerful tool that can be effectively used to study binding mechanisms involving a cryptic site, where ligand binding requires a large conformational change in the protein to occur.

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