Modeling and docking antibody structures with Rosetta

ABSTRACT We describe Rosetta-based computational protocols for predicting the three-dimensional structure of an antibody from sequence and then docking the antibody–protein-antigen complexes. Antibody modeling leverages canonical loop conformations to graft large segments from experimentally-determined structures as well as (1) energetic calculations to minimize loops, (2) docking methodology to refine the V L –V H relative orientation, and (3) de novo prediction of the elusive complementarity determining region (CDR) H3 loop. To alleviate model uncertainty, antibody–antigen docking resamples CDR loop conformations and can use multiple models to represent an ensemble of conformations for the antibody, the antigen or both. These protocols can be run fully-automated via the ROSIE web server or manually on a computer with user control of individual steps. For best results, the protocol requires roughly 2,500 CPU-hours for antibody modeling and 250 CPU-hours for antibody–antigen docking. Tasks can be completed in under a day by using public supercomputers.