期刊
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
卷 82, 期 -, 页码 157-166出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jmgm.2018.04.015
关键词
VEGF; Protein-glycosaminoglycan interactions; Molecular docking; Replica exchange molecular dynamics; Circular dichroism spectroscopy
类别
资金
- National Science Center of Poland (Narodowe Centrum Nauki) [UMO-2016/21/P/ST4/03995]
- European Union's Horizon, 2020 research and innovation programme under the Marie Sklodowska-Curie grant [665778]
- German Research Council [SFB-TRR67]
- Hungarian Momentum programme [LP2016-2]
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. (C) 2018 Elsevier Inc. All rights reserved.
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