ADVANCED QUANTUM MECHANICAL SCREENING OF LEADS AGAINST PERIODONTITIS DRUG TARGET CYSTALYSIN FROM TREPONEMA DENTICOLA.

Alhobeira, Hazza A.

Hemolytic protein, Cystalysin from Treponema denticola, is a known drug target for combating Periodontitis. Cystalysin catalyzes the release of hydrogen sulphide and ammonia which is responsible for tissue hemolysis and conversion of hemoglobin to sulfhemoglobin and methemoglobin in periodontal pockets. In the present study we have performed an exhaustive screening of Natural Product Library to identify potential Leads (drug like molecules) that may inhibit the hemolytic action of this enzyme. Natural product library was screened to identify top 50 potential binders by LibDock tool followed by RMSD filtration. These were then subjected to advanced Quantum Mechanical Molecular Mechanical (QM/MM) docking on pipeline pilot. Four most promising ligands are reported along with their binding stability scores and interaction patterns. Two of the four inhibitors NP-015209 and NP-020109 appear to be the most promising leads since they specifically interact with the functionally active amino acids at the active site thereby blocking the catalytic action of the enzyme (Cystalysin). These inhibitors appear to be most promising leads for drug development against periodontitis.

TREPONEMA denticola; PERIODONTITIS treatment; DRUG development; DRUG target; METHEMOGLOBIN

Biochemical & Cellular Archives, 2019, Vol 19, Issue 2, p3513

0972-5075

Academic Journal

10.35124/bca.2019.19.2.3513