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

Abstract

We 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.
Author Urszula Uciechowska-Kaczmarzyk (FCh / DTCh / LMM)
Urszula Uciechowska-Kaczmarzyk,,
- Laboratory of Molecular Modeling
, Sándor Babik
Sándor Babik,,
-
, Ferenc Zsila
Ferenc Zsila,,
-
, Krzysztof Bojarski (FCh / DTCh / LMM)
Krzysztof Bojarski ,,
- Laboratory of Molecular Modeling
, Tamás Beke-Somfai
Tamás Beke-Somfai,,
-
, Sergey Samsonov (FCh / DTCh / LMM)
Sergey Samsonov,,
- Laboratory of Molecular Modeling
Journal seriesJournal of Molecular Graphics & Modelling, ISSN 1093-3263, (A 25 pkt)
Issue year2018
Vol82
Pages157-166
Publication size in sheets0.5
Keywords in Englishprotein-glycosaminoglycan interactions, molecular docking, replica exchange molecular dynamics, circular dichroism spectroscopy
DOIDOI:10.1016/j.jmgm.2018.04.015
URL https://doi.org/10.1016/j.jmgm.2018.04.015
Languageen angielski
Score (nominal)25
ScoreMinisterial score = 25.0, 31-08-2018, ArticleFromJournal
Ministerial score (2013-2016) = 25.0, 31-08-2018, ArticleFromJournal
Publication indicators WoS Impact Factor: 2016 = 1.754 (2) - 2016=1.813 (5)
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