Background: Matrix metalloproteinase-8 (MMP-8) participates in the degradation of different
types of collagens in the extracellular matrix and basement membrane. Up-regulation of the
MMP-8 has been demonstrated in many 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 a
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 the degree of each of the amino acids in the ligand-amino acid interaction network for
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 bioinformatics web tools. Post-docking analyses were performed using BIOVIA Discovery
Studio Visualizer version 220.127.116.1187.
Results and Discussion: According to results, 24 of the studied compounds were 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, and 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.