Targeted CDR Library Design¶
Targeted CDR Library Design is a task to design a CDR library de novo target a given epitope. It is especially useful when you want to design an antibody that targets a specific epitope, but you don't have a good starting point. It is also useful when you want to explore the potential targeting strategies to an epitope.
Challenges¶
The search space for such a library design is huge as we need to determine the amino acid types and positions of more than ten residues in the paratope while considering the possible intra-antibody and epitope-paratope interactions. Traditional methods could hardly balance efficiency and accuracy.
Features¶
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De novo design: You only need to choose an antibody framework. The HCDR3 region is designed de novo according to the target epitope.
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Sequence-structure co-design: Our unique sequence-structure co-design algorithm is skilled at generating multiple candidate antibody sequences and the corresponding predicted complex structures.
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Cutting-edge algorithm: Based on our proprietary generative and geometric AI models, our design algorithm achieves state-of-the-art performance on both sequence recovery and structure alignment.
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Friendly interface: You can directly select the epitope from the antigen structure using the Structure Viewer. The whole process is graphical, smooth and intuitive.
Inputs¶
To submit a Targeted CDR Library Design job, open the Project Editor and select "Targeted CDR Library Design" from the "Design" dropdown menu.
- Antigen: The target antigen.
- Structure: Target antigen structure in PDB/mmCIF format. The structure can be uploaded from a local machine, imported from a cloud database or generated by a GeoBiologics job.
- Epitope: A set of residues comprising the epitope of the antigen. Input a comma-separated list of contiguous sequence fragments with the format
{chain}:{start_res}-{end_res}, e.g.,A:2-10,A:15-30,B:40-100. You could also select the epitope from the antigen structure using the Structure Viewer and click on "import from selection" to fill in this input box automatically.
- Antibody: An antibody with the CDR region to be designed.
- Antibody Name: Name of the antibody. Defaults to "Antibody". To change it, hover above the antibody name, and click on the "
" button. - Sequence: Sequence of the antibody template. The HCDR3 region to be designed should be replaced by the placeholder
[H3, {len}], where {len} is the desired length of the HCDR3 region. Below is an example. 
(Upload Sequence): Upload your own antibody template (a .FASTA file) by clicking the "" button. Your antibody template must have 2 chains with labels ending with "_H" and "_L" respectively. Above is an example.- Switch template: Here are some highly-developable antibody templates for you to choose from.
- Antibody Name: Name of the antibody. Defaults to "Antibody". To change it, hover above the antibody name, and click on the "
- Job Name: Name of the job. Note that the job name must be unique within the project.
Models & Parameters¶
GeoAbDesign, our proprietary HCDR3 design model, is available for this job. Parameters of this model are as follows.
- # designs: The number of sequences to generate (default to 10).
- temp: Temperature for antibody sequence sampling (default to 0.9).
- seed: Random seed for structure initialization (default to a random integer).
- Relax structure: Whether to relax the model-generated protein using Amber (default to false).
Results¶
Click the job name in the Files & Jobs panel to view the job results.
The result summary is stored in a CSV file, which can be downloaded by clicking the "
" button to the top-right of the Summary Table.
The summary table contains the following columns:
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name: Name of the designed antibodies. The i-th design is named
seq{i}. -
vh_sequence: Protein sequence of the (designed) heavy chain variable domain.
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vl_sequence: Protein sequence of the light chain variable domain.
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H3_designed_sequence: Designed sequence for HCDR3 region. All designed sequences have a length of {len} as specified in the antibody template.
In the rightmost column, you could click on the "
" button to view the structure of the designed antibody with the target antigen.
If you enabled the "relax" option, you would find two files in the dropdown menu: one for the unrelaxed structure and one for the relaxed structure.
