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 nc1 domain fragment of the α3 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 3-kinase (pi3k), protein kinase b (pkb/akt) and mammalian target of rapamycin (mtor) signaling pathway. in addition, it prevents the dissociation of eukaryotic initiation factor 4e protein (eif4e) from 4e binding protein1 through interaction with integrins like αᵥβ3. methods: in the present study, we used cluspro docking server version 2.0 to evaluate interaction of tumstatin (pdb id: 5nb0) to receptors including full-length mmp2 (pdb id: 1ck7), αᵥβ3 (pdb id: 3ije), α5β1 (pdb id: 3vi3) and vegfr2 (pdb id: 1vr2). 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 1000 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 ???3, vegfr2, ?5?1, and mmp2 with lowest binding energy of -1215.1, -1105.3, -1083.4, and -1082.1, respectively. conclusion: therefore, tumstatin binds to αᵥβ3 stronger than other receptors emphasizing the importance of inhibition of signaling pathway through αᵥβ3 integrin in the prevention of angiogenesis.