scholarly journals Binding of Chlorinated Phenylacrylonitriles to the Aryl Hydrocarbon Receptor: Computational Docking and Molecular Dynamics Simulations

2019 ◽  
Author(s):  
Stefan Paula ◽  
Jennifer R. Baker ◽  
Xiao Zhu ◽  
Adam McCluskey
Keyword(s):  
Molecular Dynamics ◽  
Aryl Hydrocarbon Receptor ◽  
Molecular Dynamics Simulations ◽  
Computational Docking ◽  
Aryl Hydrocarbon ◽  
Dynamics Simulations

scholarly journals Positive allosteric modulators of lecithin: Cholesterol acyltransferase adjust the orientation of the membrane-binding domain and alter its spatial free energy profile

2021 ◽  
Vol 17 (3) ◽  
pp. e1008426
Author(s):  
Akseli Niemelä ◽  
Artturi Koivuniemi
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Membrane Binding ◽  
Binding Domain ◽  
Esterification Reaction ◽  
Allosteric Modulators ◽  
Allosteric Site ◽  
Computational Docking ◽  
Positive Allosteric Modulators ◽  
Dynamics Simulations

Lecithin:cholesterol acyltransferase protein (LCAT) promotes the esterification reaction between cholesterol and phospholipid-derived acyl chains. Positive allosteric modulators have been developed to treat LCAT deficiencies and, plausibly, also cardiovascular diseases in the future. The mechanism of action of these compounds is poorly understood. Here computational docking and atomistic molecular dynamics simulations were utilized to study the interactions between LCAT and the activating compounds. Results indicate that all drugs bind to the allosteric binding pocket in the membrane-binding domain in a similar fashion. The presence of the compounds in the allosteric site results in a distinct spatial orientation and sampling of the membrane-binding domain (MBD). The MBD’s different spatial arrangement plausibly affects the lid’s movement from closed to open state and vice versa, as suggested by steered molecular dynamics simulations.

Sign in / Sign up

Export Citation Format

Share Document