Molecular dynamics-based model of VEGF-A and its heparin interactions
Urszula Uciechowska-Kaczmarzyk , Sándor Babik , Ferenc Zsila , Krzysztof Bojarski , Tamás Beke-Somfai , Sergey Samsonov
AbstractWe present a computational model of the Vascular Endothelial Growth Factor (VEGF), an important regulator of blood vessels formation, which function is affected by its heparin interactions. Although structures of a receptor binding (RBD) and a heparin binding domain (HBD) of VEGF are known, there are structural data neither on the 12 amino acids interdomain linker nor on its complexes with heparin. We apply molecular docking and molecular dynamics techniques combined with circular dichroism spectroscopy to model the full structure of the dimeric VEGF and to propose putative molecular mechanisms underlying the function of VEGF/VEGF receptors/heparin system. We show that both the conformational flexibility of the linker and the formation of HBD-heparin-HBD sandwich-like structures regulate the mutual disposition of HBDs and so affect the VEGF-mediated signalling.
|Journal series||Journal of Molecular Graphics & Modelling, ISSN 1093-3263, (A 25 pkt)|
|Publication size in sheets||0.5|
|Keywords in English||protein-glycosaminoglycan interactions, molecular docking, replica exchange molecular dynamics, circular dichroism spectroscopy|
|Score|| = 25.0, ArticleFromJournal|
= 25.0, ArticleFromJournal
|Publication indicators||: 2017 = 1.885 (2) - 2017=1.806 (5)|
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