Fig. 1: Molecular dynamics simulation of DH270.6 association with a truncated CH848 HIV-1 Env gp120.
From: Engineering immunogens that select for specific mutations in HIV broadly neutralizing antibodies
A Schematic representation of an antibody Fv and gp120 antigen associating through an intermediate encounter ensemble. Transition rates k1 and k-1 represent the ensemble rate of forming a collision-induced encounter state and dissociating to the unbound conformation, respectively, while k2 describes the conversion rate from an encounter intermediate to the bound complex. B (left) An HIV-1 Env trimer ectodomain structure. The protomer on the left highlights gp120 (blue) allosteric elements V1/V2 (green), V3 (red), β20- β21 (yellow), as well as gp41 (orange). The protomer to the right highlights the gp120 region that is extracted (gp120T) from the prefusion closed state structure (orange) and gp41 (purple). The third protomer of the trimer is represented in a gray surface. (middle) The Man9 glycosylated gp120T highlights the position of the N332-glycan (green surface). (right) The Man9 glycosylated gp120T with the DH270.6 antibody Fv positioned near the N332-glycan. C RMSD trajectories (light blue) of three representative transitions from encounter states to the bound state. Distances between DH270.6 heavy chain R57 and gp120 D325 (black) show close interactions (<3.0 Å, red line) before reaching the bound state. D Representative encounter to bound transition showing rotation of the DH270.6 Fv (fade from red to white to blue) around the N332-glycan (purple/red spheres). E Frames from the representative simulations in an R57 to D325 interactive encounter transition (top) and the final, non-interactive R57 to D325 bound state. Source data are provided as a Source Data file.
