Molecular Docking and Simulation Analysis of Glioblastoma Cell Surface Receptors and Their Ligands: Identification of Inhibitory Drugs Targeting Fibronectin Ligand to Potentially Halt Glioblastoma Pathogenesis

Glioblastoma (GB) is an aggressive brain cancer with high microvascular proliferation. The pathological angiogenesis leads to accelerated tumour invasion and diffused infiltration into the surrounding brain tissues, with a tragically short survival rate. Various transmembrane proteins, which are embedded on the glioblastoma cancer cell surface, interact with diverse extracellular ligands/molecules present in the tumor micro-environment. These ligands play a crucial role in the development, progression, and therapeutic resistance. In the present study, we systematically screened multiple transmembrane protein receptors, and their extracellular ligands involved/implicated in GB cancer cell progression. Additionally, we analyzed the homotypic and heterotypic protein associations within glioblastoma cancer cells to better understand their role in tumor development. Ten well-known and clinically approved GB cancer drugs were selected and retrieved from online databases for molecular docking analyses with extracellular proteins. Among the different ligands analyzed, computational analysis revealed a strong interaction between fibronectin (PDB ID: 3VI4) and the majority of GB surface receptors. Furthermore, molecular docking studies between GB-approved drugs and fibronectin demonstrated the strongest binding interaction with Irinotecan, followed by Etoposide, Vincristine, etc. In conclusion, identification of ligand-drugs interactions provides valuable insights into the mechanisms underlying GB cancer cell development and potential avenues for therapeutic inhibition strategies. Our study demonstrated that Irinotecan, Etoposide, and Vincristine exhibit strong binding interactions with fibronectin, effectively disrupting its interaction with surface receptor(s). Since fibronectin receptor interactions play a crucial role in GB tumor progression, these findings suggest that targeting fibronectin could present a promising strategy to inhibit GB cell proliferation and invasion.