An expanded benchmark for antibody-antigen docking and affinity prediction reveals insights into antibody recognition determinants.
An expanded benchmark for antibody-antigen docking and affinity prediction reveals insights into antibody recognition determinants.
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DOI：
10.1016/j.str.2021.01.005
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发表时间：
2021-06-03
期刊：
影响因子：
--
通讯作者：
Pierce BG
中科院分区：
文献类型：
--
作者：
Guest JD;Vreven T;Zhou J;Moal I;Jeliazkov JR;Gray JJ;Weng Z;Pierce BG
抗体-抗原复合物结构的准确预测模型和基于结构的抗体设计仍然是计算生物学的主要挑战，对生物治疗、免疫和疫苗具有影响。通过系统地搜索抗体-抗原复合物的高分辨率结构以及未结合的抗体和抗原结构，结合实验确定的结合亲和力的鉴定，我们组装了一组用于抗体-抗原对接和亲和力预测的非冗余测试用例。该基准使我们之前的基准中可用的抗体-抗原复合物和相应亲和力的数量增加了一倍以上，提供了对抗体识别的决定因素的前所未有的看法以及对分子灵活性的见解。对对接和亲和力预测工具的初步评估强调了这组不同案例所带来的挑战，其中包括骆驼纳米抗体、治疗性单克隆抗体和针对病毒糖蛋白的广泛中和抗体。该数据集将为这种治疗相关的蛋白质-蛋白质相互作用类别开发先进的预测模型和设计方法。预测性抗体-抗原对接和基于结构的设计代表了计算生物学中长期存在且在治疗上重要的挑战。客人等人。组装了大量非冗余的抗体-抗原测试用例，具有高分辨率的结合和非结合结构以及结合亲和力，以实现该领域的高级算法开发和基准测试。
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. Predictive antibody-antigen docking and structure-based design represent longstanding and therapeutically important challenges in computational biology. Guest et al. assembled a large and nonredundant set of antibody-antigen test cases, with high resolution bound and unbound structures and binding affinities, to enable advanced algorithm developments and benchmarking in this area.
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