RosettaSurf—A surface-centric computational design approach
Fig 5
Surface centric design of a viral antigenic site present the in RSVF.
A) Design process of site 0-mimicking protein scaffolds. Starting scaffolds are selected from the PDB based on structural alignments with the epitope helix. The surface mimicking designs are generated by grafting the side chains of the helix segment of the epitope onto the scaffold and surface-centric design is employed to optimize the loop region. Before and after design of the surface compared to native site 0. Blue areas indicate high similarity. B) Mimicry of surface geometry of WT scaffold, RSV_FixBB, and Surf_03 designs compared to native site 0. C) Representative SPR measurements of Surf_03 and RSV_FixBB against site 0-specific antibodies D25 and ADI14496. D) Binding profiles of Surf_03, a FixBB designed protein, and a helix-only design against a panel of site-specific antibodies with green indicating binding and red cells corresponding to non-binding. A knockout mutant of Surf_03 and the WT protein binding profiles are listed as reference.