AntibodyDesignMover

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AntibodyDesignMover

Author

Jared Adolf-Bryfogle; jadolfbr@gmail.com; PI: Roland Dunbrack

Part of the RosettaAntibody and RosettaAntibodyDesign (RAbD) Framework

Rosetta Antibody Design (RAbD) Manual

Purpose

Runs the full Rosetta Antibody Design (RAbD) mover. Requires an AHo numbered antibody. Note that only the top design will move on in RosettaScripts. See the Rosetta Antibody Design (RAbD) Manual for more information. Note that the AntibodyDesignProtocol runs the AntibodyDesignMover, but has a simpler interface. Any antibody design options discussed in the antibody design documentation but not set through the XML (as outlined in this document) can be set through the Command line.

Basic Options

Sequence Design

Generally, one would want to do a simple run that optimizes the interface energy and uses cluster-based profiles for sequence design:

<AntibodyDesignMover seq_design_cdrs="(&string (ex: L1,L1,L3))" mc_optimize_dG="1"/>

Graft Design

If you want to explore different loop conformations of different CDRs, you can use the graft_design_cdrs option to graft these on from the database and refine. You may use any combination of sequence and graft design CDRs. There are many more options, like being able to limit the length, or staying within the current cluster. In order to control these, you would pass a cdr_instruction_file. See the full RAbD manual for more: RosettaAntibodyDesign#antibody-design-cdr-instruction-file

<AntibodyDesignMover graft_design_cdrs="(&string (ex: L1,L1,L3))" seq_design_cdrs="(&string (ex: L1,L1,L3))" mc_optimize_dG="1"/>

Full Options

Autogenerated Tag Syntax Documentation:

Author: Jared Adolf-Bryfogle (jadolfbr@gmail.com) Main mover of RosettaAntibodyDesign (RAbD). One can set seq_design_cdrs if only sequence designing CDRs (which will use CDR cluster-profiles by default) and/or graft_design_cdrs to control which CDRs graft-designed through integrated antibody database sampling(if any). A cdr instruction file can be set to further limit these options or set only specific lengths or clusters to be designed. The interface will be analyzed at the end of the protocol and information added to the scorefile. light_chain must be set either in the tag or on the cmd-line. Please see the RAbD Manual for more information.

References and author information for the AntibodyDesignMover mover:

AntibodyDesignMover Mover's citation(s): Adolf-Bryfogle J, Kalyuzhniy O, Kubitz M, Weitzner BD, Hu X, Adachi Y, Schief WR, and Dunbrack Jr RL Jr. (2018). RosettaAntibodyDesign (RAbD): A general framework for computational antibody design. PLoS Comput Biol 14(4):e1006112. doi: 10.1371/journal.pcbi.1006112.

<AntibodyDesignMover name="(&string;)" min_scorefxn="(&string;)"
        atom_pair_cst_weight="(&real;)" dihedral_cst_weight="(&real;)"
        global_atom_pair_cst_scoring="(&bool;)" scorefxn="(&string;)"
        global_dihedral_cst_scoring="(&bool;)" light_chain="(&string;)"
        seq_design_cdrs="(&string;)" graft_design_cdrs="(&string;)"
        mintype="(&string;)" instruction_file="(&string;)"
        mc_optimize_dG="(false &bool;)" mc_interface_weight="(1.0 &real;)"
        mc_total_weight="(0.0 &real;)" do_dock="(&bool;)"
        dock_first_cycles="(2 &positive_integer;)"
        dock_second_cycles="(2 &positive_integer;)" use_epitope_csts="(&bool;)"
        epitope_residues="(&string;)" paratope_cdrs="(&string;)"
        random_start="(&bool;)"
        design_protocol="(EVEN_CLUSTER_MC &ABdesign_protocols;)"
        primary_cdrs="(&string;)" dock_cycles="(&non_negative_integer;)"
        interface_dis="(&real;)" neighbor_dis="(&real;)"
        outer_cycles="(&non_negative_integer;)"
        relax_cycles="(&non_negative_integer;)"
        inner_cycles="(&non_negative_integer;)"
        mutate_framework_for_cluster="(&bool;)" outer_kt="(&real;)"
        inner_kt="(&real;)" top_designs="(&non_negative_integer;)"
        run_AIM="(&bool;)" remove_antigen="(&bool;)" />

min_scorefxn: Name of score function to use for minimization
atom_pair_cst_weight: Weight for atom pair constraints to use in the antibody design minimization score function
dihedral_cst_weight: Weight for dihedral constraints to use in the antibody design minimization score function
global_atom_pair_cst_scoring: Use atom pair constraints in the antibody design minimization score function?
scorefxn: Name of score function to use
global_dihedral_cst_scoring: Score dihedral constraints to use in the global antibody design score function?
light_chain: Set the light chain if not a camelid antibody. If not set here, it must be set on the cmd-line
seq_design_cdrs: CDR regions to be Sequence-Designed
graft_design_cdrs: CDR regions to be Graft-Designed
mintype: Set the mintype for all designign CDRs. Default min. Can be set individually in the CDR instructions file. relax is much more intensive, but takes significantly longer Understood Options: legal = [min, cartmin, relax, backrub, pack, dualspace_relax, cen_relax, none]
instruction_file: Path to the CDR instruction file (see application documentation for format)
mc_optimize_dG: Optimize the dG during MonteCarlo. dG is calculated by InterfaceAnalyzer. It is not possible to do this within overall scoring, but where possible, do this during MC calls. This option results in better dGs. See the options mc_interface_weight and mc_total_weight to control the components of each to the score. Default is interface weight at 1.0, total weight at 0.
mc_interface_weight: Weight of interface score (dG) if using mc_optimize_dG
mc_total_weight: Weight of the classic total score if using mc_optimize_dG
do_dock: Run RosettaDock during the inner cycles? Significantly increases run time. Default False
dock_first_cycles: First set of High-res dock cycles. Default in Full Docking protocol is 4.
dock_second_cycles: Second set of High-res dock cycles. Default in Full Docking protocol is 45.
use_epitope_csts: Use the ParatopeEpitopeSiteConstraintMover during design instead of just the ParatopeSiteConstraintMover. Default False
epitope_residues: Use these residues as the epitope residues. Adds site constraints for dock-design. (auto-detects by default ). Comma separated.
paratope_cdrs: Use these CDRs for Paratope Constraints instead of all of them. Useful if attempting to create or optimize the interface of a specific CDR, or keep a CDR in contact with a region of antigen. Comma separated. List of CDR regions (string) devided by one of the following characters: ":,'`~+*|;. "Recognized CDRs: "Aroop|Chothia|Kabat|Martin|North|"
random_start: Start with random CDRs from the antibody design database for any undergoing GraftDesign
design_protocol: Sets the design protocol (see app documentation for more information)
primary_cdrs: Manually set the CDRs which can be chosen in the outer cycle. These should be on for either Sequence-Design or Graft-Design. Normally, the outer cycles are whatever CDRs we are designing, including CDRs which are sequence-design only.
Use this if you are primarily interested in specific CDRs (such as graft-designing H3 and allowing H1 and L3 to sequence design during the inner cycle.)
dock_cycles: Change the number of time the dock protocol is run
interface_dis: Set the interface detection distance. Default 8A
neighbor_dis: Set the neighbor detection distance. Default 6A
outer_cycles: Set the number of outer cycles. Default 25.
relax_cycles: Set the number of relax cycles. Default 5.
inner_cycles: Set the number of inner (minimization) cycles. Default 1.
mutate_framework_for_cluster: Should we add framework mutations for the specified cdr? Default True.
outer_kt: Temperature to use for outer cycle. Default 1.0
inner_kt: Temperature to use for inner cycle. Default 1.0
top_designs: Number of top designs to keep. Default is 1
run_AIM: Run InterfaceAnalyzer at the end of the protocol on the pose? Default True
remove_antigen: Removes antigen at the very beginning of the protocol. Default False

AntibodyDesignMover