Design C3-symmetric oligomers to bind the SARS-CoV-2 Spike protein.

[lipan6461188]

Dear developers, I am repeating the analysis of "Design of C3-symmetric oligomers to scaffold the binding interface of the designed ACE2 mimic". But I found RFDiffusion may change the orientation of motif protomer.

Data link: https://drive.google.com/drive/folders/19BZTqTx-uKEjVqGp06Ez2zufb7hgva-q?usp=share_link

The file 7uhc.pdb has been centrelized by me can been accessed from this link. I used Chimera to prove it is C3 symmetry along z axis:

open 7uhc.pdb
delete #0:.B #0:.C #0:.E #0:.F
sym #0 group C3 axis z
open 7uhc.pdb

Then I used RFDiffusion to design the C3-symmetric oligomers with following command:

run_inference.py \
    inference.symmetry=C3 \
    inference.num_designs=1 \
    inference.output_prefix=Spike_Symmetric_PPI/1_structure_design/Spike_Symmetric_PPI_1.0_0.1_Base \
    'potentials.guiding_potentials=["type:olig_contacts,weight_intra:1.0,weight_inter:0.1"]' \
    potentials.olig_intra_all=True \
    potentials.olig_inter_all=True \
    potentials.guide_scale=2 \
    diffuser.T=50 \
    potentials.guide_decay=quadratic \
    inference.input_pdb=7uhc.pdb \
    'contigmap.contigs=[D1-55/120/0 E1-55/120/0 F1-55/120/0]' \
    inference.ckpt_override_path=models/Base_ckpt.pt

The output file can be accessed from this link. And I open 7uhc.pdb and Spike_Symmetric_PPI_1.0_0.1_Base_0.pdb with Chimera:

open 7uhc.pdb
open Spike_Symmetric_PPI_1.0_0.1_Base_0.pdb
delete #0:.A #0:.B #0:.C
display @CA
~ribbon

And I align model #1 to model #0:

 mm #0 #1

Only one motif can be perfectly matched.

[thomas-tugwell]

@lipan6461188 bumping for visibility.

Did you solve this issue? I'm having this same issue, symmetric motifs are not fixed in place it seems. I am working to find the relevant code in the source to correct the behavior, but would be glad if someone already fixed this.

EDIT 3/30/25: For anyone interested, this fork (mostly) solves the issue for me: RFdiffusion-symmetric-motif-RMSD-check