Antibody Sequences to 3D Models

Category Paths

Follow one of these paths in the Orion user interface, to find the floe.

  • Product-based/AbXtract

  • Product-based/SZMAP

  • Role-based/Computational Chemist

  • Role-based/Structural Biologist

  • Role-based/Bioinformatician

  • Solution-based/Virtual-screening/Target Preparation

  • Solution-based/Hit to Lead/Target Preparation/Structural Data Preparation

  • Solution-based/Biologics/Antibody Design/Target Preparation/Structure Prediction

  • Solution-based/Biologics/Antibody Design/Target Preparation/Surface Patch Analysis

  • Task-based/Target Prep & Analysis/Protein Preparation

Description

This floe uses the ImmuneBuilder structure prediction ML model to generate 3D antibody structures from sequence data. These structures are then used to generate an OEDesignUnit that has been styled and annotated for use in antibody applications and downstream modeling.

Heavy and light chains will be identified from the antibody’s sequence data and named accordingly. A naming scheme (from a selection of IMGT, Chothia, Martin, or Kabat) will be applied to the antibody’s residues and numbered accordingly. The resulting design unit’s styling will identify the different CDR regions and label the structure’s liabilities including motifs associated with post and co-translational modifications.

By default, patch analysis will also be run on the structure. Patch analysis defines patch surface(s) based on hydrophobicity and/or charge and can optionally calculate SZMAP surfaces. Additional styling shows all residues that are in proximity to the default hydrophobic patch method.

ImmuneBuilder is a third-party antibody structure prediction method by OPIG. For more information, see ImmuneBuilder .

Potential Input Sources: Import Antibody FASTA Files Floe

Related Floes: Antibody Surface Patch Generation, Antibody Experimental Structure Prep, and Antibody MD Simulations with Conformational Analysis Floes

Computational Cost Scaling: Sequence to structure prediction can be highly parallelized. For best performance, batch many antibody sequence pairs in a single floe run.

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 is RESNAME:RESNUM:ICODE:CHAINID[:FRAGNO:ALTLOC] - 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’]

Patch Analysis Options

Patch and Property Analysis (switch): Option to run patch hydrophobicity and antibody property calculations.

  • Required

  • Type: boolean

  • Default: True

  • Choices: [True, False]

Style DU Based on Hydrophobicity (style_du): All residues that are in proximity to the hydrophobic surface will have the wireframe atom style. If multiple surfaces are detected, the first method/scale pair from the selection menu will be used to style the protein.

  • Required

  • Type: boolean

  • Default: True

  • Choices: [True, False]

Hydrophobic Patch Method(s) (method_names): Sets how hydrophobic patches are calculated. When viewing the patches in the 3D viewer, green are hydrophobic, and purple are hydrophilic patches.

  • Type: string

  • Default: [‘SAP’]

  • Choices: [‘SAP’, ‘SASA’, ‘Sequence’]

Hydrophobic Patch Scale(s) (scale_names): Sets the scaling scheme(s) for hydrophobic patch calculation. All selected scales are dependent on the Hydrophobic Patch Method parameter.

  • Type: string

  • Default: [‘Jain’]

  • Choices: [‘Jain’, ‘Bandyopadhyaya-Mehler’, ‘Eisenberg’, ‘Meek’, ‘Rose’, ‘Wimley-White’, ‘Miyazawa’, ‘Black-Mould’, ‘Kyte-Doolittle’]

Hydrophobic Patches (style_hydro_patch): Style the hydrophobic surface(s) using patches instead of displaying the entire surface.

  • Required

  • Type: boolean

  • Default: True

  • Choices: [True, False]

Charge Surface Method(s) (charge_method_names): Sets how charged patches are calculated. When viewing the patches in the 3D viewer, red are positively charged, and blue are negatively charged patches.

  • Type: string

  • Default: [‘Formal Charge Electrostatic Potential’]

  • Choices: [‘Formal Charge Electrostatic Potential’, ‘Electrostatic Potential’]

Charge Patches (style_charged_patch): Style the charge surface(s) using patches instead of displaying the entire surface.

  • Required

  • Type: boolean

  • Default: False

  • Choices: [True, False]

Patch Cutoff (patch_cutoff): Patch cutoff percent of the max value that will be used to identify a patches. Anything below the indicated percent will be cutoff. Values should range between 0.0 and 0.95.

  • Type: decimal

  • Default: 0.4

Inputs

Input Dataset of Sequences (in): Two fields on this dataset are necessary to run the floe. One field should contain the variable heavy sequence, and on another field the variable light sequence.

  • Type: data_source

VH Sequence Field (vh_seq): Field on the input dataset containing the variable heavy chain sequence.

  • Required

  • Type: field_parameter::string

VL Sequence Field (vl_seq): Field on the input dataset containing the variable light chain sequence.

  • Required

  • Type: field_parameter::string

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

Sequence Numbering Scheme (numbering_scheme): This parameter sets the numbering scheme applied to antibodies.

  • Required

  • Type: string

  • Default: IMGT

  • Choices: [‘IMGT’, ‘Chothia’, ‘Martin’, ‘Kabat’]

Style Liabilities (style_liabs): Option to style known liability patterns.

  • Required

  • Type: boolean

  • Default: True

  • Choices: [True, False]

Outputs

Output Dataset of Antibody Structure Models (out): Antibody model(s) will be design unit(s) annotated using the selected sequence numbering scheme.

  • Required

  • Type: dataset_out

  • Default: Antibody_Models

Failed Sequence Output (failed_out): Any sequences that cannot adhere to the selected sequence numbering scheme will fail.

  • Required

  • Type: dataset_out

  • Default: failed_antibody_sequences