Overview of Symmetry in RFD3

Specifying symmetry in your input specifications

Symmetry configurations are specified within the input JSON or YAML file, nested under its own specific configuration. The symmetry specific config has the following:

"symmetry": {
    "id": "C3",
    "is_unsym_motif": "Y1-11,Z16-25",
    "is_symmetric_motif": true

}

symmetry:
    id: "C3"
    is_unsym_motif: "Y1-11,Z16-25"
    is_symmetric_motif: true

• id : Symmetry group ID; e.g. “C3” for a cyclic protein with 3 subunits, “D2” for a dihedral protein with 2 subunits. Note that only C and D symmetry types are supported currently.

• is_unsym_motif : Comma separated string list of contig/ligand names that should NOT be symmetrized (e.g. DNA strands). If not provided, all motifs are assumed to be symmetrized. See Designs with motifs section for details.

• is_symmetric_motif: Boolean value whether the input motif is symmetric. Currently only symmetric input motifs are supported, therefore, true by default.

Example command

You can run the following example command:

./src/modelhub/inference.py inference_sampler.kind=symmetry out_dir=logs/inference_outs/sym_demo/0 ckpt_path=$cur_ckpt inputs=./projects/aa_design/tests/test_data/sym_tests.json diffusion_batch_size=1 

• inference_sampler.kind: Set symmetry to tern on symmetry mode.

• diffusion_batch_size : 8 by default, but it is recommended to set it to 1 for symmetry due to memory limitations.

• low_memory_mode : Additionally you can set this to True if you have memory constraints (e.g. “CUDA error: out of memory”). However, this will significantly slow the inference.

Unconditional multimer design

As mentioned above, we currently only support C and D symmetry types. The following provides a general overview of the types of symmetry and examples of how to run:

Cyclic

Defaults:

{
    "uncond_C5": {
        "length": 100,
        "is_non_loopy": true,
        "symmetry": {
            "id": "C5"
        }
    }
}

Dihedrals

Defaults:

{
    "uncond_D4": { 
        "length": 50,
        "is_non_loopy": true,
        "symmetry": {
            "id": "D4"
        }
    }
}

Designs with motifs

As mentioned above, symmetry sampling currently only supports pre-symmetrized motifs around the origin. Therefore, is_symmetric_motif is set to true by default. The following are example JSON specifications for different symmetric motif scaffolding. You can also find the corresponding input PDBs in docs/input_pdbs/symmetry_examples. Although we only give JSON examples, you can also use YAML for everything shown below.

The tasks that these examples describe are as follows:

• unindexed_C2_1j79, unindexed_C2_1e3v: Unindexed motif scaffolding for symmetric enzyme active sites. The motifs are located within a subunit; no inter-subunit motifs.

• indexed_unsym_C2_1bfr: Indexed motif scaffolding for a single active site held by a symmetric enzyme. is_unsym_motif specifies the ligand that shouldn’t be symmetrized.

• uncond_unsym_C3_6t8h: Unconditional generation of C3 proteins around a DNA helix. The DNA chains are the motifs. is_unsym_motif specifies the DNA strands that shouldn’t be symmetrized.

{
    "unindexed_C2_1j79": {
        "symmetry": {
            "id": "C2",
            "is_symmetric_motif": true
        },
        "input": "../input_pdbs/symmetry_examples/1j79_C2.pdb",
        "ligand": "ORO,ZN",
        "unindex": "A250",
        "length": 130,
        "select_fixed_atoms": {
            "A250": "OD1,CG"
        }
    },
    "unindexed_C2_1e3v": {
        "symmetry": {
            "id": "C2",
            "is_symmetric_motif": true
        },
        "input": "../input_pdbs/symmetry_examples/1e3v_C2.pdb",
        "ligand": "DXC",
        "unindex": "A16,A40,A100,A103",
        "length": 80,
        "select_fixed_atoms": {
            "A16": "OH,CZ,CE1,CE2",
            "A40": "OD2,CG",
            "A100": "N,CA,C,CB",
            "A103": "OD2,CG"
        }
    },
    "indexed_unsym_C2_1bfr": {
        "symmetry": {
            "id": "C2",
            "is_symmetric_motif": true,
            "is_unsym_motif": "HEM"
        },
        "input": "../input_pdbs/symmetry_examples/1bfr_C2.pdb",
        "ligand": "HEM",
        "contig": "51,M52,80",
        "length": null,
        "select_fixed_atoms": {
            "M52": "CG,SD,CE"
        }
    },
    "unsym_C3_6t8h": {
        "symmetry": {
            "id": "C3",
            "is_symmetric_motif": true,
            "is_unsym_motif": "Y1-11,Z16-25"
        },
        "input": "../input_pdbs/symmetry_examples/6t8h_C3.pdb",
        "contig": "150-150,/0,Y1-11,/0,Z16-25",
        "length": null,
        "is_non_loopy": true
    }
}