In silico analysis for metalloenzyme-protein interactions applied to MMP8-Fibronectin 1 and MMP12-Factor XII
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Keywords:
Metalloenzymes, Molecular docking, Protein-protein interactions, Metalloenzyme-substrate complex, ProteolysisAbstract
The prediction of the proteolytic susceptibility of the metalloenzyme-target protein complexes has been a little-explored field of protein-protein interactions (PPI). Thus, the development and application of bioinformatics tools focused on proteolytic propensity and molecular docking are needed. This study correlated the predictive ability of PROSPER and protein-protein docking tools for the identification of cleavage sites of known zinc-metalloprotease substrates. Human interaction complexes MMP8-Fibronectin 1 and MMP12-Factor XII were evaluated, and the comparative docking analysis was performed using ClusPro, BioLuminate, and PatchDock programs. According to the results, the sequences with the highest probability of proteolytic propensity proposed by PROSPER coincided with up to 50% of the true positives of the TOP10 solution obtained in ClusPro and BioLuminate. However, in PatchDock favorable results were not obtained. Finally, the solvation of MMP8-Fibronectin in the WaterMap tool showed the interaction of Zn+2 with water molecules in the active site of the enzyme. The results were comparable with the usual proteolytic mechanism of zinc metalloproteases. In conclusion, this is a novel study that proposed powerful tools for the in silico prediction of the interaction of metalloenzymes and target proteins, because of their high predictive power. In addition, with the support of protein-protein interaction networks, the discovery of new targets could be facilitated.
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