Molecular Dynamic Stability Study of VEGF Inhibitor in Patients with Bladder Cancer.

Abstract

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.