schrödinger molecular modeling suite  (Molecular Dynamics Inc)

Journal: The Journal of Biological Chemistry

Article Title: Mechanism of Sirt1 NAD + -dependent Protein Deacetylase Inhibition by Cysteine S -Nitrosation *

doi: 10.1074/jbc.M116.754655

Figure Lengend Snippet: Molecular dynamics simulations support an allosteric mechanism of Sirt1 inhibition by S-nitrosation. 100-ns molecular dynamics simulations of Sirt1 WT, Sirt1-SNO, and Sirt1 C395S/C398S were performed using the Schrödinger Maestro molecular dynamics modeling platform. a, RMSF of each residue was calculated using Schrödinger Maestro and plotted against residue number. b, RMSF values of Sirt1-SNO and Sirt1 C395S/C398S were subtracted from Sirt1 WT RMSF values. ΔRMSF values within 1 S.D. of the average difference in RMSF were excluded, revealing localized regions of significant dynamic change between wild-type and modified Sirt1. c, differences in Sirt1-SNO or Sirt1 C395S/C398S RMSF outside of 1 S.D. plotted in b were mapped to the crystal structure of Sirt1 with ADP-ribose bound (PDB code 4KXQ (33)). Residues colored green indicate predicted regions of increased dynamics in Sirt1-SNO and Sirt1 C395S/C398S. Residues colored purple indicate predicted regions of increased rigidity in Sirt1-SNO and Sirt1 C395S/C398S. d, aligned end point structures from the Sirt1 WT (black), Sirt1-SNO (blue), and Sirt1 C395S/C398S (red) molecular dynamics simulations. The gray arrow represents the observed tilting away of the Zn2+-tetrathiolate subdomain relative to the Rossmann-fold subdomain in Sirt1-SNO and Sirt1 C395S/C398S compared with Sirt1 WT.

Article Snippet: Conformational dynamics of Sirt1 WT, S -nitrosated Sirt1 (Sirt1-SNO), and Sirt1 C395S/C398S were simulated using the Schrödinger Maestro molecular dynamics modeling suite using the OPSL3 force field.

Techniques: Inhibition, Residue, Modification