Molecular Modeling and Docking Studies on the First Chlorotoxin-Like Peptide from Iranian Scorpion Mesobuthuseupeus (Meict) and SNP Variants of Matrix Methaloproteinase-2 (MMP-2)

Background: MeICT is the first chlorotoxin-like peptide isolated from the Iranian Scorpion Mesobuthus eupeus. Chlorotoxin (CTX) is a neurotoxin that specially binds to (MMP-2) on ma-lignant cells and now is used in treatment of glioma. In the present study, we have used homology modeling to propose the 3D structure of MeICTand analyze its interaction with MMP-2 and its SNP types. Methods:The structure of MeICT was modeled by using homology modeling through the Swiss-Model workspace. Structural evaluation and stereo-chemical analysis of modeled struc-ture of MeICT was performed using ProSA-web Z-scores and Mol Probity Ramachandran plots. Hex Server was used to investigate the interactions between MeICT and catalytic domain of MMP-2 and SNP types. Binding energies calculation and complementarity scores were used for evaluation of protein docking. Results:The comparable Z-scores, Ramachandran plot characteristics and RMSD values confirmed the quality of the homology model of MeICT. About 17 SNP variants in catalytic domain of MMP2 were detected. According to the total and electrostatic energies and the number of interactive residues by hydrogen bond, the structure of MeICT-rs200271857, MeICT-rs144334568, MeICT-rs111590299 and MeICT-rs201083413complexes are more stable. Conclusion: The structure of MeICT is similar to CTX, somight be used as therapeutic agent in glioma. We could find some variants of MMP-2 that can bind to MeICT with more or less af-finity and can affect treatment pathway.