Molecular dynamics simulation of sirt1 inhibitor from indonesian herbal database

Objective: Sirtuins are protein deacetylases regulating cellular metabolism, lifespan, stress responses, and linked with diseases pathogenesis such as cancer and neurodegenerative diseases. SIRT1, one of human seven sirtuins, the most widely studied today. Hence, identification of SIRT1 drug compound has attracted in drug discovery community. To find good drug candidates could use in insilico methods as a quick tool for analyzing the biological activity of drugs virtually. Method: In silico methods in this research using molecular dynamics simulations that use Indonesia herbal database to identification hits compounds as the SIRT1 inhibitor. Analysis of molecular dynamics simulations in this study includes RMSD (root mean square deviation), RMSF (root mean square fluctuation), molecular mechanism Poisson-Boltzmann/surface area (MMPBSA) and hydrogen bonding. Results: The results showed that hits compounds, dregamine and 5-oxo-coronaridine against two of macromolecules SIRT1 (PDB ID: 4I5I and 4ZZI) obtained free energy MMPBSA calculation about -23 kcal/mol Meanwhile occupancy hydrogen bonding of residues Ile347 and Asp348 about 80%. Conclusion: Hits compounds dregamine and 5-oxocoronaridine against two of macromolecules SIRT1 inhibitor (PDB ID: 4I5I and 4ZZI) obtained free energy MMPBSA calculation about -23 kcal/mol meanwhile occupancy hydrogen bonding of residues Ile347 and Asp348 about 80%.