Comparing the binding energies and inhibition constant of sunitinib malate-metal complex on tyrosine kinase receptor by computational molecular docking

Sunitinib malate is an oral multikinase inhibitor used in the treatment of renal cell carcinoma and other cancers, including gastrointestinal stromal tumors. Protein-ligand docking studies are widely used to predict the binding affinity of ligands. The binding of bivalent metals is expected to enhance the ligand's binding affinity to the protein. CB-Dock software is one of the commercial tools available for protein-ligand docking. The main objective of this study is to estimate the binding affinity of the Sunitinib malate drug to the tyrosine kinase protein. Additionally, the study aims to determine if the binding affinity increases when Sunitinib malate is complexed with different bivalent metals (Cu, Fe, Zn). Docking studies were conducted between Sunitinib malate and the tyrosine kinase receptor using CB-Dock software. The binding affinities of Sunitinib malate and its complexes with copper, iron, and zinc were evaluated. The binding affinity of Sunitinib malate alone to tyrosine kinase was found to be -7.1. When complexed with copper, the binding affinity improved to -7.5. However, the binding affinities for the Sunitinib-iron and Sunitinib-zinc complexes were -6.9 and -6.8, respectively. From the data, it can be concluded that the Sunitinib malate-copper complex demonstrates a higher binding affinity (-7.5) compared to Sunitinib malate alone (-7.1) and its complexes with iron (-6.9) and zinc (-6.8). Therefore, the Sunitinib-copper complex can be optimized for formulations to enhance its binding affinity and drug-targeting efficiency.