Table 1.
List of selected hit molecules and their docking score.
Fig 1.
Structural representation of docked compounds in the binding pocket of SIRT1.
(A) Cartoon representation of SIRT1 with Doxercalciferol (magenta) and Timiperone (cyan) along with the reference inhibitor Selisistat (green). (B) Surface potential view of SIRT1 binding pocket occupied by the selected compounds and Selisistat.
Fig 2.
2D structural representation of SIRT1 residues interacting with (A) Doxercalciferol, (B) Timiperone, and (C) Selisistat.
Table 2.
List of selected compounds and their biological properties calculated through PASS webserver.
Pa, probability to be active; Pi, probability to be inactive.
Fig 3.
Structural dynamics and compactness of SIRT1 upon Doxercalciferol and Timiperone binding as a function of time.
(A) RMSD plot of SIRT1 in complex with Doxercalciferol and Timiperone. (B) Residual fluctuations (RMSF) plot of SIRT1 before and after Doxercalciferol and Timiperone binding. (C) Time evolution of radius of gyration (Rg). (D) SASA plot of SIRT1 as a function of time.
Fig 4.
Intramolecular hydrogen bonding.
(A) Time evolution and stability of hydrogen bonds (H-bonds) formed within 0.35 nm Intra-SIRT1 before and after Doxercalciferol and Timiperone binding. (B) The probability distribution function (PDF) of the H-Bonds for both the systems.
Fig 5.
Intermolecular hydrogen bonding.
(A) The time evolution plot shows the formation of intermolecular hydrogen bonds between SIRT1 and Doxercalciferol. (B) The plot shows PDF of SIRT1 and Doxercalciferol hydrogen bonds. (C) Time evolution plot of hydrogen bonds between SIRT1 and Timiperone. (D) PDF plot of hydrogen bonds between SIRT1 and Timiperone.
Fig 6.
Secondary structure dynamics of (A) free SIRT1, (B) SIRT1-Doxercalciferol, and (C) SIRT1-Timiperone. The secondary structure content in SIRT1 is the sum of α-helix, β-sheet, β-bridge, and turns.
Fig 7.
(A) 2D projections of trajectories on eigenvectors (EVs) showing conformational projections of SIRT1, SIRT1-Doxercalciferol and SIRT1-Timiperone (B) The time-evolution of projections of trajectories on both EVs.
Fig 8.
The Gibbs free energy landscapes for (A) free SIRT1 (B) SIRT1-Doxercalciferol and Timiperone.