@article{812fade0110d4ad5b9b7c826ba7f7f18,
title = "An expanded benchmark for antibody-antigen docking and affinity prediction reveals insights into antibody recognition determinants",
abstract = "Accurate predictive modeling of antibody-antigen complex structures and structure-based antibody design remain major challenges in computational biology, with implications for biotherapeutics, immunity, and vaccines. Through a systematic search for high-resolution structures of antibody-antigen complexes and unbound antibody and antigen structures, in conjunction with identification of experimentally determined binding affinities, we have assembled a non-redundant set of test cases for antibody-antigen docking and affinity prediction. This benchmark more than doubles the number of antibody-antigen complexes and corresponding affinities available in our previous benchmarks, providing an unprecedented view of the determinants of antibody recognition and insights into molecular flexibility. Initial assessments of docking and affinity prediction tools highlight the challenges posed by this diverse set of cases, which includes camelid nanobodies, therapeutic monoclonal antibodies, and broadly neutralizing antibodies targeting viral glycoproteins. This dataset will enable development of advanced predictive modeling and design methods for this therapeutically relevant class of protein-protein interactions.",
keywords = "affinity prediction, antibody design, biotherapeutics, monoclonal antibodies, nanobody, protein-protein docking, viruses",
author = "Guest, {Johnathan D.} and Thom Vreven and Jing Zhou and Iain Moal and Jeliazkov, {Jeliazko R.} and Gray, {Jeffrey J.} and Zhiping Weng and Pierce, {Brian G.}",
note = "Funding Information: We thank the authors of the experimental binding affinity measurements who kindly provided information on experimental conditions to our team, for the subset of cases for which temperature values or other details were not found in the literature. We also thank the many structural biologists whose work resulted in this large and diverse set of experimentally determined high-resolution structures. Arjan van der Velde (University of Massachusetts Medical School) and Ragul Gowthaman (University of Maryland IBBR) provided assistance with website implementation. Docking calculations for ZDOCK, ZRANK, and SnugDock were performed using the Institute for Bioscience and Biotechnology Research computing facility, the Maryland Advanced Research Computing Center, Texas Advanced Computing Center at the University of Texas at Austin, and the Extreme Science and Engineering Discovery Environment, which is supported by National Science Foundation grant number TG-MCB130184. This work was supported by startup funding from the University of Maryland (to B.G.P.), NIH R01 GM126299 (to B.G.P.), NIH R01 GM116960 (to Z.W.), NIH R01 GM078221 (to J.J.G. and J.R.J.), F31 GM123616 (to J.R.J.), and NIH R21 AI135701 (to J.J.G. and J.Z.). J.D.G. was supported in part by the University of Maryland Virology Program graduate training grant (NIH T32 AI125186). I.M. was supported by GlaxoSmithKline. Conceptualization, J.D.G. T.V. Z.W. and B.G.P.; Methodology, J.D.G. T.V. J.Z. J.R.J. J.J.G. Z.W. and B.G.P.; Data Curation, J.D.G. T.V. J.Z. I.M. and B.G.P.; Investigation, J.D.G. T.V. J.Z. and B.G.P.; Writing – Original Draft, J.D.G. J.Z. and B.G.P.; Writing – Review & Editing, all authors. I.M. is employed by GlaxoSmithKline plc, which discovers and sells antibody therapies. Z.W. is a cofounder of Rgenta Therapeutics and serves on its scientific advisory board. J.J.G. is an unpaid board member of the Rosetta Commons. Under institutional participation agreements between the University of Washington, acting on behalf of the Rosetta Commons, Johns Hopkins University may be entitled to a portion of revenue received on licensing Rosetta software, including some methods described in this article. As a member of the Scientific Advisory Board, J.J.G. has a financial interest in Cyrus Biotechnology. Cyrus Biotechnology distributes the Rosetta software, which includes methods described in this article. These arrangements have been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. Funding Information: We thank the authors of the experimental binding affinity measurements who kindly provided information on experimental conditions to our team, for the subset of cases for which temperature values or other details were not found in the literature. We also thank the many structural biologists whose work resulted in this large and diverse set of experimentally determined high-resolution structures. Arjan van der Velde (University of Massachusetts Medical School) and Ragul Gowthaman (University of Maryland IBBR) provided assistance with website implementation. Docking calculations for ZDOCK, ZRANK, and SnugDock were performed using the Institute for Bioscience and Biotechnology Research computing facility, the Maryland Advanced Research Computing Center, Texas Advanced Computing Center at the University of Texas at Austin, and the Extreme Science and Engineering Discovery Environment , which is supported by National Science Foundation grant number TG-MCB130184 . This work was supported by startup funding from the University of Maryland (to B.G.P.), NIH R01 GM126299 (to B.G.P.), NIH R01 GM116960 (to Z.W.), NIH R01 GM078221 (to J.J.G. and J.R.J.), F31 GM123616 (to J.R.J.), and NIH R21 AI135701 (to J.J.G. and J.Z.). J.D.G. was supported in part by the University of Maryland Virology Program graduate training grant ( NIH T32 AI125186 ). I.M. was supported by GlaxoSmithKline . Publisher Copyright: {\textcopyright} 2021 Elsevier Ltd",
year = "2021",
month = jun,
day = "3",
doi = "10.1016/j.str.2021.01.005",
language = "English (US)",
volume = "29",
pages = "606--621.e5",
journal = "Structure",
issn = "0969-2126",
publisher = "Cell Press",
number = "6",
}