Structural Studies on an Anti-Angiogenic Peptide Using Molecular Modeling

Document Type : Research Paper


1 Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran

2 Department of Life Sciences Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran

3 Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran; Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran


Background: Development of VEGF antagonists, which inhibit its interaction with the receptors, is a widely used strategy for the inhibition of angiogenesis and tumor growth.
Objectives: In the present study, a VEGFR-1 antagonistic peptide was designed and its potential for binding to VEGFR-1 and VEGFR-2 was evaluated by theoretical studies.
Materials and Methods: Based on the X-ray structure of VEGF-B/VEGFR-1 D2 (PDB ID: 2XAC), an antagonistic peptide (known as VGB1) was designed, and its model structure was constructed using homology modeling in the MODELLER, version 9.16. The validity of the modeled structures was estimated employing several web tools. Finally, one model was
chosen and molecular dynamics (MD) simulation was applied using the GROMACS package, version 5.1.4, to allow conformational relaxation of the structure. Next, docking process of the peptide with VEGFR-1 and VEGFR-2 was performed by HADDOCK web server and the docking structures were optimized by MD simulation for 20 ns. The far-UV circular
dichroism (CD) spectrum of VGB1 was recorded to evaluate the overall structure of the peptide.
Results: The far-UV CD spectrum indicated that VGB1 contains α helix structure. The results from docking studies suggested that Van der Waals and nonpolar interactions play the most important role in the peptide binding to VEGFR-1. In addition, our results implicated the relevance of both Van der Waals and electrostatic interactions in the formation of complex between VGB1 and VEGFR-2. In addition to the common binding residues in the corresponding region of VEGF-A and VEGF-B, additional binding residues also were predicted for the interaction of VGB1 with VEGFR-1 and VEGFR-2.
Conclusions: The results of MD and molecular docking simulations predicted that VGB1 recognizes both VEGFR-1 and VEGFR-2, which may lead to the prevention of the downstream signaling triggered by these receptors.


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