Molecular Docking Study for Inhibitors of Aggregatibacter actinomycetamcomitans Toxins in Treatment of Aggressive Perioodontitis

Introduction: Periodontitis is a chronic inflammatory disease of the periodontal tissues causing periodontal attachment loss and destruction of the alveolar bone which leads to mobility and loss of teeth. Aggregatibacter actinomycetemcomitans (Aa) is a gram negative, capnophilic, coccobacillus that plays an important role in aggressive Periodontitis. Aa produces a variety of virulence factors that facilitate the colonization, invasion and destruction of the periodontal tissues. Leukotoxin and cytolethal distending toxin (Cdt) are most important virulence factors of Aa.

Materials and methods: The three dimensional structure of leukotoxin was derived by Easy modeller software and Cdt was retrieved from RCSB database. The possible binding sites of toxins were searched using binding site prediction tool Q site finder. A total of 1000 ligands of flavanol derivatives were generated with the help of software ACD chemsketch. Rapid virtual screenings of these compounds were performed in the docking tool iGEMDOCK v2.0. Based on the binding energy, six ligands were selected for the further study. The selected six ligands were then analysed for drug relevant properties based on "Lipinski's rule of five" and other drug like properties. The accurate docking of six ligands was performed using docking tool iGEMDOCK v2.0.

Results: From the present study, it has been found that carboxyl {(2R,3R)-3,7 dihydroxy 4-oxo-2(3,4,5-trihydroxyphenyl)-3,4-dihydro2H-chromen-5-yl} oxonium, which is a novel compound can effectively act as an inhibitor for both the toxins.

Conclusion: The leucotoxin and cytolethal distending toxin of Aa is found to be the major virulence factors involved in the causation of aggressive periodontitis. Hence the inhibitors of these toxins can be an effective drug in treatment of aggressive periodontitis.