Homology modeling, Molecular Dynamic Simulation and in silico screening of Activator for the Intensification of human sirtuin type 1 (SIRT1) by novel 1, 3, 4-thiadiazole derivatives-A potential antiaging approach

Sirtuin type-1(SIRT1) is a regulator of various biosynthetic pathways via activation of peroxisome proliferator-activated receptor-γ and interacting with adenosine-mono-phosphate kinase. SIRT1 is the important target for various neurodegenerative, cancer and metabolic disorders as well as aging medicine. Keeping in view of the above fact, we considered novel 1,3,4-thiadiazole derivatives series for SIRT1 screening, which was performed through virtual screening,  homological modeling, docking and computational studies. On the basis of available molecular structure in protein data bank of SIRT1 protein, we calculated the interaction energy designed molecules. The interaction energy of designed compound VR3 closely better than resveratrol (̴ 6.4 kcal/mol). Among of them the VR 3 shown the best conformation fitting stability in the binding site of SIRT1 predicted by MD (Molecular dynamics) simulation for 2.5ns. Therefore, the designed compounds have good binding affinities to SIRT1 target, would serve better lead compound for antiaging screening for future drug design perspective.