Experimental antibody engineering often involves generation and screening of antibody libraries targeting a specific antigen. To supplement the screening process, we developed and tested a Rosetta-based cross-docking method for separation of cognate and non-cognate antigen-antibody complexes. After refining each candidate structure to optimize the energy of the non-cognate complexes and erase the memory of the crystal structure, we used the RosettaDock interface score to distinguish the cognate antibody from the non-cognate antibodies. Over the complete dataset, cognate complexes are among the top two lowest-scoring structures in 15 of 17 cases when using bound structures, and 7 of 17 cases when using unbound structures. The method also identifies some cognate antigen-antibody pairs when the rigid-body conformational sampling is extended to include global searches. We will report the effect of tuning the RosettaDock score function to maximize the free energy gap between cognate and non-cognate complexes on the accuracy of predictions.

Cross-docking to identify antibody-antigen interaction partners

245th National Meeting (2013)

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