Molecular Dynamics Simulation of SIRT1 Inhibitor from Indonesian Herbal Database

Abstract

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-oxocoronaridine 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%. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

A Comparative Linear Interaction Energy and MM/PBSA Study on SIRT1–Ligand Binding Free Energy Calculation

“…Analogous to previous MD studies, 31,40 the SIRT1 crystal structure with PDB ID 4I5I(41) was used as the protein template structure for docking and subsequent MD. Along with the protein atom coordinates, the positions of the zinc ion and one of the water molecules in the binding pocket 31 were retained to obtain the template.…”