Structural basis and energy landscape of apigenin-induced cancer cell apoptosis mechanism in PI3K/Akt pathway

This study attempted to elucidate how apigenin (AGI) interferes with the PI3K/Akt pathway to fulfill its anti-tumour activity by anchoring on the ATP-binding pocket of PI3K and PDK1. The structural basis and energetic property of AGI and ATP binding to human PDK1 and PI3K isoforms α, β, γ and δ were...

Full description

Saved in:
Bibliographic Details
Published inMolecular simulation Vol. 42; no. 2; pp. 138 - 148
Main Authors Duan, Ruizhi, Tian, Feifei, Sun, Jiaoyang
Format Journal Article
LanguageEnglish
Published Taylor & Francis 22.01.2016
Subjects
ADMET
apigenin
Binding energy
Entropy
flexible docking
Human
Mathematical models
Molecular dynamics
PI3K/Akt pathway
Pocket
Simulation
Online AccessGet full text

Cover

More Information
Summary:This study attempted to elucidate how apigenin (AGI) interferes with the PI3K/Akt pathway to fulfill its anti-tumour activity by anchoring on the ATP-binding pocket of PI3K and PDK1. The structural basis and energetic property of AGI and ATP binding to human PDK1 and PI3K isoforms α, β, γ and δ were investigated in detail with homology modelling and molecular docking. Free binding energy calculations and molecular dynamics simulations revealed that AGI can cause less conformational entropy loss than ATP upon the binding and possess the same level of binding stability with that of ATP. Combining ADMET prediction, AGI was evaluated as a strong ATP-competitive inhibitor with good pharmacokinetics profile.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0892-7022
1029-0435
DOI:10.1080/08927022.2015.1021346