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Updated: May 13, 2025
Mouse Bladder Wall Injection
Published on: July 12, 2011
Molecular Dynamic Stability Study of VEGF Inhibitor in Patients with Bladder Cancer
Ginanda Putra Siregar1, Ida Parwati1, Tjahjodjati Tjahjodjati1
1Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia.
Background:
Vascular endothelial growth factor (VEGF) plays a crucial role in bladder cancer progression. Brolucizumab, an anti-VEGF agent, has been studied in various diseases; however, its potential in bladder cancer remains largely unexplored.
Objective:
This study aimed to analyze the molecular docking and dynamic stability of Brolucizumab as a VEGF inhibitor in bladder cancer.
Methods:
Target protein and ligand data mining were conducted. Proteins were prepared by removing water molecules using Discovery Studio 2019. Ligand energy minimization was performed using Pyrx v.0.9.8. Protein-ligand docking was conducted, and protein-protein docking was performed using the HADDOCK server. The interactions between compounds and proteins were visualized with BioVia Discovery Studio 2019. Molecular dynamics simulations were carried out using the YASARA Dynamic program.
Results:
Brolucizumab binding induced smaller conformational changes compared to VEGFR2 binding. When VEGFR2 interacted with the VEGFA-Brolucizumab complex, significant conformational changes occurred, suggesting an inhibitory and blocking effect of Brolucizumab. Bond relaxation was observed when Brolucizumab bound to VEGFA and VEGFR, initiating conformational changes as part of its inhibitory activity. Brolucizumab demonstrated strong and competitive binding to VEGFA, with greater affinity than VEGFR2.
Conclusion:
Brolucizumab exhibits inhibitory and blocking activity against VEGFR2, suggesting its potential as a therapeutic agent in bladder cancer.
Insights
Brolucizumab shows potential as a bladder cancer therapeutic by strongly inhibiting vascular endothelial growth factor receptor 2 (VEGFR2). Molecular simulations reveal its effective binding and blocking action against VEGFR2, crucial for cancer growth.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Vascular endothelial growth factor (VEGF) is vital for bladder cancer progression.
- Brolucizumab, an anti-VEGF agent, has potential therapeutic applications in bladder cancer, though largely unexplored.
Purpose of the Study:
- To investigate the molecular docking and dynamic stability of Brolucizumab as a VEGF inhibitor in bladder cancer.
- To analyze Brolucizumab's interaction with VEGFA and VEGFR2 at a molecular level.
Main Methods:
- Utilized molecular docking and dynamic simulations (Discovery Studio, Pyrx, HADDOCK, YASARA).
- Performed protein-ligand and protein-protein docking to assess binding interactions.
- Analyzed conformational changes and binding affinities.
Main Results:
- Brolucizumab binding induced distinct conformational changes in VEGFR2, indicating an inhibitory effect.
- Brolucizumab demonstrated strong, competitive binding to VEGFA with higher affinity than VEGFR2.
- Observed bond relaxation and conformational shifts upon Brolucizumab binding to VEGFA and VEGFR2.
Conclusions:
- Brolucizumab exhibits significant inhibitory and blocking activity against VEGFR2.
- Brolucizumab shows promise as a potential therapeutic agent for bladder cancer treatment.
