Studying of the interaction of tumstatin with some receptors by molecular docking simulations

Background and Aim: Inhibition of angiogenesis is one promising treating strategies of cancer. Tumstatin, an NC۱ domain fragment of the α۳ chain of type IV collagen, is an endogenous anti-angiogenic and pro-apoptotic protein. Tumstatin binds to some receptors on the endothelial cell surface and acts through activation of focal adhesion kinase (FAK), phosphoinositol ۳-kinase (PI۳K), protein kinase B (PKB/AKT) and mammalian target of rapamycin (mTOR) signaling pathway. In addition, it prevents the dissociation of eukaryotic initiation factor ۴E protein (eIF۴E) from ۴E binding protein۱ through interaction with integrins like αᵥβ۳.Methods: In the present study, we used ClusPro docking server version ۲.۰ to evaluate interaction of tumstatin (PDB ID: ۵NB۰) to receptors including full-length MMP۲ (PDB ID: ۱CK۷), αᵥβ۳ (PDB ID: ۳IJE), α۵β۱ (PDB ID: ۳VI۳) and VEGFR۲ (PDB ID: ۱VR۲). ClusPro is a fully automated web server for the prediction of protein–protein interactions. The program recruits PIPER, a FFT based rigid docking program to generate ۱۰۰۰ low energy docked conformations using pairwise interaction potentials. The best complex consisting of the lowest energy and maximum cluster member was analyzed and visualized by PyMol. In addition, residues involving in the interaction were determined by PyMol.Results: Results showed that tumstatin bind to ???۳, VEGFR۲, ?۵?۱, and MMP۲ with lowest binding energy of -۱۲۱۵.۱, -۱۱۰۵.۳, -۱۰۸۳.۴, and -۱۰۸۲.۱, respectively.Conclusion: Therefore, tumstatin binds to αᵥβ۳ stronger than other receptors emphasizing the importance of inhibition of signaling pathway through αᵥβ۳ integrin in the prevention of angiogenesis.

Keywords:

Tumstatin , ClusPro , Receptor , Low energy