Last edited 4/25/2013. Corresponding PI Jeffrey Gray (firstname.lastname@example.org).
Application source code:
Main mover source code:
To see demos of some different use cases see integration tests located in
rosetta/rosetta_tests/integration/antibody_protocol_* (antibody_protocol_using_KIC_loop_mover, antibody_protocol_using_CCD_loop_mover).
To run Rosetta3Antibody, type the following in a command line:
[path to executable]/antibody_model_CDR_H3.[platform|linux/mac][compile|gcc/ixx]release –database [path to database] @options
Note: these demos will only generate one decoy. To generate a large number of decoys you will need to add –nstruct N (where N is the number of decoys to build) to the list of flags.
We recommend the following articles for further studies of RosettaDock methodology and applications:
B. D. Weitnzer*, J. R. Jeliazkov*, S. Lyskov*, N. Marze, D. Kuroda, R. Frick, J. Adolf-Bryfogle, N. Biswas, R. L. Dubrack Jr, & J. J. Gray, "Modeling and docking of antibody structures with Rosetta," Nature Protocols 12, 401–216 (2017)
J. Xu, D. Kuroda & J. J. Gray, “RosettaAntibody3: Object-Oriented Designed Protocol and Improved Antibody Homology Modeling.” (2013) in preparation
Determine the structure of antibody homology models by combining VL-VH docking (using docking protocol) and H3 loop modeling (loop modeling protocol ).
Sample command line (as of May 17th, 2020):
# input grafted model -s grafting/model-0.relaxed.pdb # recommended number of structs -nstruct 1000 # constraints are enabled by default, so flags are shown just to indicate that they can be turned off # recommended as kink is present in 90% of Abs and as VH-VL Q-Q is present in 808% -antibody:h3_loop_csts_lr true -antibody:h3_loop_csts_hr true -antibody:auto_generate_h3_kink_constraint true -antibody:constrain_vlvh_qq true -constraints:cst_weight 1.0 # standard settings, for packages used by antibody_H3 -ex1 -ex2 -extrachi_cutoff 0 # necessary if running multiple procs w/o MPI -multiple_processes_writing_to_one_directory # specify output file -out:file:scorefile H3_modeling_scores.fasc # specify output folder -out:path:pdb H3_modeling
Detailed Description of Flags (may not have been included above):
-antibody:h3_loop_csts_lr true -antibody:h3_loop_csts_hr true -antibody:auto_generate_h3_kink_constraint true -antibody:constrain_vlvh_qq true
AtomPair CD 38L CD 39H LINEAR\_PENALTY 4.1 0 0.4 400
Additional Description of constraint file:
AtomPair CD 38L CD 39H LINEAR_PENALTY 4.1 0 0.4 400 1. To constrain two GLN, one is on L chain, the other is on H chain, they form Hydrogen bond at the L-H interface 2. “CD” is the the carbon on GLN bonding to Nitrogen and Oxygen 3. 38L means L chain 38, and 39H means H chain 39. They are GLN forming hydrogen bond. 4. LINEAR_PENALTY potential, see details in constraint file 5. distance_constraint=4.1, well_depth=0, width=0.4, slope=400, see the details in constraint file.
One antibody PDB structure with modeled H3 loop and optimized VL-VH orientation.
This is the first public release in Rosetta3
Antibody Applications: Homepage for antibody applications
Antibody Design Strategy Analysis: A PyRosetta-based tool to analyze and/or compare antibody design strategies.
CDR Cluster Identification: An application that matches each CDR of an antibody to North/Dunbrack CDR clusters based on the lowest dihedral distance to each cluster center.