Objective: The importance of SIRT1 activator’s role in antidiabetic and anti-aging therapies is widely demonstrated. Drug discovery and development are time consuming. Drug design can be performed in silico using molecular dynamic approaches to accelerate and facilitate identification of the best compound candidates and their physicochemical characteristics and hit-to-lead selection. Methods: In silico study of SIRT1 activator for complexes using of Protein Data Bank (PDB) IDs 4ZZI, 4ZZJ 4ZZH, and 5BTR and 4TO ligand. Ligand– receptor interactions and bond energies were determined using molecular docking with the AutoDock4Zn program. Then, the complex with the best bond energy was identified using a simulation of the molecular dynamics (50 ns) using the Amber program, and values for root mean square deviation, root mean square fluctuation, and bond energy were determined using the Molecular Mechanic–Poisson Boltzmann (Generalized Born) surface area (MM-PB[GB]SA) calculation. Results: Interaction analysis between activator ligand (4TO) and the SIRT1 receptor (PDB IDs 4ZZJ and 5BTR) revealed the ligand’s selectivity for hydrophobic interaction at Leu206, Ile223, Ile227, and hydrophilic interaction at Asn226, Glu230. Hydrogen bond interactions between Glu230 and Arg234 (allosteric region) with Arg446, Val459, His473, and Asp475 (catalytic region) brought them close to the bounding substrate area. Bond energy values obtained using the MM-GB(PB)SA calculation showed 4TO interaction with 4ZZJ (MMGBSA ΔG, −31.4729–−26.6756; MMPBSA ΔG, −32.6292–−28.486]. The bond energy value of the 4TO interaction with 5BTR showed MMGBSA ΔG = −40.6255–−30.0653 and MMPBSA ΔG = −34.6713–−25.9951. Conclusions: These findings provide important information on the target interaction of the bonds to the more selective SIRT1 activator useful for drug discovery and development.
- Molecular docking
- Molecular dynamic
- Molecular mechanic/Poisson Boltzmann (generalized born) surface area
- SIRT1 activator