Extended Data Fig. 3: Molecular dynamics simulation of S-nitrosylation of ACE2.
From: Targeted protein S-nitrosylation of ACE2 inhibits SARS-CoV-2 infection
a, Molecular representation of the S-nitrosylated-ACE2/RBD model upon transient detachment at the level of the peptidase domain dimeric interface. SNO-Cys261 and SNO-Cys498 are shown with Van der Waals spheres. The black dots indicate qualitative placement of centers of mass (COM) for each ACE2 protomer, and the dashed arrow represents the distance between COMs. Spike’s RBDs and N-glycans, which were included in the simulation, are hidden for image clarity. SpBD, Spike binding domain; CLD, collectrin-like domain; PD, peptidase domain. b, Distribution of the distance between COMs from molecular dynamics simulations of WT ACE2/RBD (purple) vs. nitrosylated-ACE2/RBD (cyan). Dashed black line at approximately 56.5 Å indicates the reference distance between COMs calculated from the cryo-EM structure (PDB: 6M17). S-Nitrosylated-ACE2/RBD shows an overall larger distance between COMs with a bimodal distribution. c, Close-up image illustrating Q175A to D136B interaction present in starting conformations of the S-nitrosylated-ACE2 system. d, Close-up image illustrating the disruption of the interaction between Q175A and D136B occurring along the dynamics of the S-nitrosylated-ACE2 system.
