Interaction of vascular endothelial growth factor and heparin quantified by single molecule force spectroscopy

Nanoscale ◽  
2020 ◽  
Vol 12 (22) ◽  
pp. 11927-11935
Author(s):  
Miaomiao Zhang ◽  
Ying Liu ◽  
Fengchao Cui ◽  
Christian Rankl ◽  
Juan Qin ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Vascular Endothelial Growth Factor ◽  
Molecular Dynamics Simulation ◽  
Growth Factor ◽  
Single Molecule ◽  
Force Spectroscopy ◽  
Dynamics Simulation ◽  
Vascular Endothelial ◽  
Single Molecule Force Spectroscopy ◽  
Endothelial Growth Factor

The interaction of VEGF165 and heparin was studied quantitatively and visually utilizing single molecule force spectroscopy and molecular dynamics simulation.

Rational Design of Anti-Angiogenic Peptides to Inhibit VEGF/VEGFR2 Interactions for Cancer Therapeutics

2021 ◽  
Vol 21 ◽  
Author(s):  
Samaneh Ghasemali ◽  
Safar Farajnia ◽  
Abolfazl Barzegar ◽  
Mohammad Rahmati-yamchi ◽  
Babak Negahdari ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Rational Design ◽  
Mutation Screening ◽  
Dynamics Simulation ◽  
Vascular Endothelial ◽  
Vegf Signaling ◽  
Endothelial Growth Factor ◽  
Vegf Signaling Pathway

Background: Angiogenesis is a critical physiological process that plays a key role in tumor progression, metastatic dissemination, and invasion. In the last two decades, the vascular endothelial growth factor (VEGF) signaling pathway has been the area of extensive researches. VEGF executes its special effects by binding to vascular endothelial growth factor receptors (VEGFRs), particularly VEGFR-2. Objective: The inhibition of VEGF/VEGFR2 interaction is known as an effective cancer therapy strategy. The current study pointed to design and model an anti-VEGF peptide based on VEGFR2 binding regions. Method: The large-scale peptide mutation screening was used to achieve a potent peptide with high binding affinity to VEGF for possible application in inhibition of VEGF/VEGFR2 interaction. The AntiCP and Peptide Ranker servers were used to generate the possible peptides library with anticancer activities and prediction of peptides bioactivity. Then, the interaction of VEGF and all library peptides were analyzed using Hex 8.0.0 and ClusPro tools. A number of six peptides with favorable docking scores were achieved. All of the best docking scores of peptides in complexes with VEGF were evaluated to confirm their stability, using molecular dynamics simulation (MD) with the help of the GROMACS software package. Results: As a result, two antiangiogenic peptides with 13 residues of PepA (NGIDFNRDFFLGL) and PepC (NGIDFNRDKFLFL) were achieved and introduced to inhibit VEGF/VEGFR2 interactions. Conclusions: In summary, this study provided new insights into peptide-based therapeutics development for targeting VEGF signaling pathway in tumor cells. PepA and PepC are recommended as potentially promising anticancer agents for further experimental evaluations.

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