Background:
Matrix metalloproteinase-8 (MMP-8) participates in degradation of different types of collagens in
the extracellular matrix and basement membrane. Up-regulation of the MMP-8 has been demonstrated in many of disorders
including cancer development, tooth caries, periodontal/peri-implant soft and hard tissue degeneration, and acute/chronic inflammation. Therefore, MMP-8 has become an encouraging target for therapeutic procedures for scientists. We carried out
molecular docking approach to study the binding affinity of 29 flavonoids, as drug candidates, with the MMP-8. Pharmacokinetic and toxicological properties of the compounds were also studied. Moreover, it was attempted to identify the most
important amino acids participating in ligand binding based on degree of each of the amino acids in the ligand-amino acid
interaction network for MMP-8.
Methods:
Three-dimensional structure of the protein was gained from the RCSB database (PDB ID: 4QKZ). AutoDock version 4.0 and Cytoscape 3.7.2 were used for molecular docking and network analysis, respectively. Notably, the inhibitor of
the protein in the crystalline structure of the 4QKZ was considered as a control test. Pharmacokinetic and toxicological features of compounds were predicted using bioinformatic web tools. Post-docking analyses were performed using BIOVIA
Discovery Studio Visualizer version 19.1.0.18287.
Results and Discussions:
According to results, 24 of the studied compounds considered to be top potential inhibitors for
MMP-8 based on their salient estimated free energy of binding and inhibition constant as compared with the control test:
Apigenin-7-glucoside, nicotiflorin, luteolin, glabridin, taxifolin, apigenin, licochalcone A, quercetin, isorhamnetin, myricetin, herbacetin, kaemferol, epicatechin, chrysin, amentoflavone, rutin, orientin, epiafzelechin, quercetin-3-rhamnoside, formononetin, isoliquiritigenin, vitexin, catechine, isoquercitrin. Moreover, His-197 was found to be the most important amino
acid involved in the ligand binding for the enzyme.
Conclusion:
The results of the current study could be used in the prevention and therapeutic procedures of a number of disorders such as cancer progression and invasion, oral diseases, and acute/chronic inflammation. Although, in vitro and in vivo
tests are inevitable in the future.
Structural Origins of Altered Spectroscopic Properties upon Ligand Binding in Proteins Containing a Fluorescent Noncanonical Amino Acid