Molecular Docking and Molecular Dynamics Analyses of Pazopanib with VEGF Receptors

Abstract

Objective: The antineoplastic agent Pazopanib is effective for treating renal cell cancer and soft tissue sarcoma. The aim of this study was to elucidate the anticancer mechanism of Pazopanib by exploring its molecular interactions with vascular endothelial growth factor receptors (VEGFRs). For this purpose, the most stable structure was determined, and molecular docking and molecular dynamics calculations of Pazopanib with VEGFR1 and VEGFR2 receptors were performed. Materials and Methods: Conformational analysis of Pazopanib was performed using VegaZZ software. Pazopanib was docked to the active sites of the VEGFR1 and VEGR2 receptors (PDB IDs: 3HNG; 3VHE) using Autodock Vina software. The molecular dynamics (MD) simulations were carried out using the YASARA v22.9.24 program with the AMBER14 force field. The anticancer, antibacterial, antifungal, and antiviral activities of the compounds were predicted using PaccMann, AntiBac-Pred, AntiFun-Pred, and AntiVir-Pred. Results: The molecular docking analysis of the Pazopanib molecule with the VEGFR1 and VEGFR2 receptors revealed a strong binding affinity of the investigated molecule towards the targets. The MD simulations, performed for Pazopanib-VEGFR1 and Pazopanib-VEGFR2 complexes showed that each docking complex and intermolecular interactions were stable throughout the simulations. Conclusion: Molecular docking simulations revealed a strong binding affinity of Pazopanib towards VEGFR1 (-8.6 kcal/mol) and VEGFR2 (-9.9 kcal/mol), indicating its efficacy in cancer treatment. During the 40-ns MD simulation of the Pazopanib-3hng and Pazopanib-3vhe complexes, we validated the stability of Pazopanib in the active sites of the receptors. The predicted anticancer, antibacterial, antifungal, and antiviral activities of Pazopanib revealed its versatile bioactivity.