Humanize Fv Antibodies
Category Paths
Follow one of these paths in the Orion user interface, to find the floe.
Role-based/Bioinformatician
Role-based/Structural Biologist
Solution-based/Biologics/Antibody Design/Generative Design
Solution-based/Biologics/Antibody Design
Description
This floes humanizes Fv antibodies using different Antibody LLMs and scores the sequences. It can be used to graft the CDR regions of the target antibodies to their closest germlines first before humanization with a LLM.
The goal of humanization is to reduce immunogeneicty of therapeutic antibodies by making them more human. This can be done by increasing similarity to the human germline and to existing human antibodies.
Related Floes: Sequences to 3D Models for Fv Antibodies
Promoted Parameters
Title in user interface (promoted name)
Minimization Parameters
Run Minimization (run_minimize): Option to run structure minimization.
Required
Type: boolean
Default: True
Choices: [True, False]
CDR Selection (cdr_selection): CDR loop regions to be flexible during structure relaxation.If none are selected entire system is marked flexible
Type: string
Default: []
Choices: [‘HCDR3’, ‘HCDR2’, ‘HCDR1’, ‘LCDR3’, ‘LCDR2’, ‘LCDR1’]
Make specified residue atoms flexible (flex_residues): Allow the atoms in the specified residues to be flexible for the minimization. Format: ‘RESNAME:RESNUM:ICODE:CHAINID[:FRAGNO:ALTLOC]’, e.g. ‘ALA:325: :A’ (note the blank/whitespace insert code). The regex ‘.*’ notation can be used as a wildcard. Separate multiple with ‘|’ delimiter.
Type: string
Flexible atom predicate (minimize_pred): Predicate to define what atoms to be flexible during the minimization, this will subset the flexible (site-)residues. Multiple selections work as OR statements.
Required
Type: string
Default: [‘All atoms’]
Choices: [‘All atoms’, ‘Heavy atoms’, ‘H atoms’, ‘Polar H atoms’, ‘Methyl H atoms’, ‘Backbone atoms’]
Inputs
Input Dataset of Sequences or Structures (in): To use sequences, two fields on this dataset are necessary to run the floe. One field should contain the variable heavy sequence, and another the variable light sequence. Structures can either be from the Antibody Sequences to 3D models floe or the Antibody Experimental Structure Prep floe. If both structures and sequences are present in the dataset, structures will be given preference.
Required
Type: data_source
Antibody Name Field (code_field): The field on the input dataset that will identify the antibody’s name. This could be a name, code, title, or other descriptor. If a unique field name is manually provided that does not exist on the input dataset, then a programmatically generated sequence antibody name will be generated in the form: ‘Antibody 1’ to ‘Antibody N’
Required
Type: field_parameter::string
VH Sequence Field (vh_seq): Field on the input dataset containing the variable heavy chain sequence.
Type: field_parameter::string
VL Sequence Field (vl_seq): Field on the input dataset containing the variable light chain sequence.
Type: field_parameter::string
Sequence Numbering Scheme (numbering_scheme): This parameter sets the numbering scheme applied to antibodies.
Required
Type: string
Default: IMGT
Choices: [‘IMGT’, ‘Chothia’, ‘Martin’, ‘Kabat’]
Outputs
Output Dataset of Humanized Antibody Sequences (out): Antibody sequences will be humanized and added as a field in a new dataset
Required
Type: dataset_out
Default: Humanized_Antibody_Sequences
Floe Report Name (floe_report_name):
Type: string
Default: Humanity Floe Report
Failed Sequence Output (failed_out): Any sequences that fail.
Required
Type: dataset_out
Default: failed_antibody_sequences
Humanization Options
Only Mutate Surface (only_mutate_surface): Only mutate residues at the surface for humanization
Type: boolean
Default: True
Choices: [True, False]
Antibody LLM (humanization_llm): The antibody LLM that will be used for humanization.
Required
Type: string
Default: Sapiens
Choices: [‘Sapiens’, ‘Ablang2’]
Iterations (iterations): Number of optimizations.
Required
Type: integer
Default: 3
Keep Original CDRs (keep_original_cdrs): Option to keep original CDRs.
Required
Type: boolean
Default: True
Choices: [True, False]
Human OASis Identity (human_oasis_identity): OASis identity at which a peptide is considered human.
Type: decimal
Default: 20.0
Germline Grafting Options
Graft CDRs onto Closest Germline (graft_onto_germline): Graft the CDR regions onto the closest V and J gene sequences
Type: boolean
Default: False
Choices: [True, False]
Backmutate Vernier Regions (backmutate_vernier_regions): Keep the vernier regions from the target antibody.
Type: boolean
Default: False
Choices: [True, False]