Molecular dynamics-based model of VEGF-A and its heparin interactions

Urszula Uciechowska-Kaczmarzyk, Sándor Babik, F. Zsila, Krzysztof Kamil Bojarski, Tamás Beke-Somfai, Sergey A. Samsonov

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)157-166
Number of pages10
JournalJournal of Molecular Graphics and Modelling
Volume82
DOIs
Publication statusPublished - Jun 1 2018

Fingerprint

heparins
Vascular Endothelial Growth Factor A
Heparin
Molecular dynamics
molecular dynamics
interactions
Circular dichroism spectroscopy
Vascular Endothelial Growth Factor Receptor
sandwich structures
blood vessels
regulators
Blood vessels
Intercellular Signaling Peptides and Proteins
dichroism
amino acids
Amino acids
flexibility
Amino Acids

Keywords

  • Circular dichroism spectroscopy
  • Molecular docking
  • Protein-glycosaminoglycan interactions
  • Replica exchange molecular dynamics
  • VEGF

ASJC Scopus subject areas

  • Spectroscopy
  • Physical and Theoretical Chemistry
  • Computer Graphics and Computer-Aided Design
  • Materials Chemistry

Cite this

Uciechowska-Kaczmarzyk, U., Babik, S., Zsila, F., Bojarski, K. K., Beke-Somfai, T., & Samsonov, S. A. (2018). Molecular dynamics-based model of VEGF-A and its heparin interactions. Journal of Molecular Graphics and Modelling, 82, 157-166. https://doi.org/10.1016/j.jmgm.2018.04.015

Molecular dynamics-based model of VEGF-A and its heparin interactions. / Uciechowska-Kaczmarzyk, Urszula; Babik, Sándor; Zsila, F.; Bojarski, Krzysztof Kamil; Beke-Somfai, Tamás; Samsonov, Sergey A.

In: Journal of Molecular Graphics and Modelling, Vol. 82, 01.06.2018, p. 157-166.

Research output: Contribution to journalArticle

Uciechowska-Kaczmarzyk, U, Babik, S, Zsila, F, Bojarski, KK, Beke-Somfai, T & Samsonov, SA 2018, 'Molecular dynamics-based model of VEGF-A and its heparin interactions', Journal of Molecular Graphics and Modelling, vol. 82, pp. 157-166. https://doi.org/10.1016/j.jmgm.2018.04.015
Uciechowska-Kaczmarzyk, Urszula ; Babik, Sándor ; Zsila, F. ; Bojarski, Krzysztof Kamil ; Beke-Somfai, Tamás ; Samsonov, Sergey A. / Molecular dynamics-based model of VEGF-A and its heparin interactions. In: Journal of Molecular Graphics and Modelling. 2018 ; Vol. 82. pp. 157-166.
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