Abstract
Present study attempts to determine efficient biogenic leads against proteolytic enzyme Cystalysin of Treponema denticola, a red complex pathogen, responsible for periodontitis. Cystalysin is known to play central role in the occurrence and progression of chronic generalized periodontitis. The method involves the preparation of library of compounds having biogenic origin from a large database of known compounds (ZINC). High throughput screening of 308035 compounds in the biogenic library was done to determine the top 100 best inhibitors depending on their binding efficiency. Top five Inhibitors were then subjected to exhaustive docking refinement to characterize the type and degree of interactions. Top inhibitors were found to undergo multiple hydrogen bonding and pi-anion interactions with active site residues critically important for the proteolytic activity of the enzyme. These inhibitors efficiently block the proteolysis due to Cystalysin and hence restrict the progression of periodontitis. Favorable ADMET properties of these ligands approve them to be used as potential drug like molecules against periodontal infections.