Robustification of RosettaAntibody and Rosetta SnugDock

• DOI: 10.1371/journal.pone.0234282
• Publication Date: 2021-03-25T20:32:04Z
• Authors: Jeliazko R. Jelia...; Rahel Frick; Jing Zhou; Jeffrey J. Gray
• Keywords: 0301 basic medicine; 0303 health sciences; Science; Q; R; Complementarity Determining Regions; Antibodies; Antigen-Antibody Reactions; Molecular Docking Simulation; 03 medical and health sciences; Medicine; Antigens; Databases, Protein; Software; Research Article

In recent years, the observed antibody sequence space has grown exponentially due to advances in high-throughput sequencing of immune receptors. The rise in sequences has not been mirrored by a rise in structures, as experimental structure determination techniques have remained low-throughput. Computational modeling, however, has the potential to close the sequence–structure gap. To achieve this goal, computational methods must be robust, fast, easy to use, and accurate. Here we report on the latest advances made in RosettaAntibody and Rosetta SnugDock—methods for antibody structure prediction and antibody–antigen docking. We simplified the user interface, expanded and automated the template database, generalized the kinematics of antibody–antigen docking (which enabled modeling of single-domain antibodies) and incorporated new loop modeling techniques. To evaluate the effects of our updates on modeling accuracy, we developed rigorous tests under a new scientific benchmarking framework within Rosetta. Benchmarking revealed that more structurally similar templates could be identified in the updated database and that SnugDock broadened its applicability without losing accuracy. However, there are further advances to be made, including increasing the accuracy and speed of CDR-H3 loop modeling, before computational approaches can accurately model any antibody.