Structure and Physicochemical Properties of the Aβ42 Tetramer: Multiscale Molecular Dynamics Simulations

2019 ◽  
Vol 123 (34) ◽  
pp. 7253-7269 ◽  
Author(s):  
Hoang Linh Nguyen ◽  
Pawel Krupa ◽  
Nguyen Minh Hai ◽  
Huynh Quang Linh ◽  
Mai Suan Li
Keyword(s):  
Molecular Dynamics ◽  
Physicochemical Properties ◽  
Molecular Dynamics Simulations ◽  
Dynamics Simulations

scholarly journals Prediction of Molecular Interactions And Physicochemical Properties Relevant For Vasopressin V2 Receptor Antagonism

2021 ◽  
Author(s):  
Ania de la Nuez Veulens ◽  
Yoanna María Álvarez Ginarte ◽  
Rolando Eduardo Rodríguez Fernandez ◽  
Fabrice Leclerc ◽  
Luis Alberto Montero Cabrera
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Physicochemical Properties ◽  
Molecular Dynamics Simulations ◽  
Binding Mode ◽  
Qsar Model ◽  
Antagonist Activity ◽  
Vasopressin V2 Receptor ◽  
V2 Receptor ◽  
Dynamics Simulations

Abstract We have developed two ligand and receptor-based computational approaches to study the physicochemical properties relevant to the biological activity of vasopressin V2 receptor (V2R) antagonist and eventually to predict the expected binding mode to V2R. The obtained Quantitative Structure Activity Relationship (QSAR) model showed a correlation of the antagonist activity with the hydration energy (EH2O) , the polarizability (P) and the calculated partial charge on atom N7 (q6) of the common substructure. The first two descriptors showed a positive contribution to antagonist activity, while the third one had a negative contribution. V2R was modeled and further relaxed on a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocoline (POPC) membrane by molecular dynamics simulations. The receptor antagonist complexes were guessed by molecular docking, and the stability of the most relevant structures were also evaluated by molecular dynamics simulations. As a result, amino acid residues Q96, W99, F105, K116, F178, A194, F307, and M311 were identified with the probably most relevant antagonist-receptor interactions on the studied complexes. The proposed QSAR model could explain the molecular properties relevant to the antagonist activity. The contributions to the antagonist-receptor interaction appeared also in agreement with the binding mode of the complexes obtained by molecular docking and Molecular Dynamics. These models will be used in further studies to look for new V2R potential antagonist molecules.

Sign in / Sign up

Export Citation Format

Share Document