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.

中文翻译：

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RosettaAntibody和Rosetta SnugDock的强化

近年来，由于免疫受体高通量测序的进展，观察到的抗体序列空间呈指数增长。序列的增加尚未反映出结构的增加，因为实验结构确定技术仍保持低通量。但是，计算建模有可能缩小序列与结构之间的差距。为了实现此目标，计算方法必须健壮，快速，易于使用且准确。在这里，我们将报告RosettaAntibody和Rosetta SnugDock的最新进展-用于抗体结构预测和抗体-抗原对接的方法。我们简化了用户界面，扩展并自动化了模板数据库，概括了抗体的运动学-抗原对接（可对单域抗体进行建模），并引入了新的环建模技术。为了评估更新对建模准确性的影响，我们在Rosetta的新科学基准框架下开发了严格的测试。基准测试表明，可以在更新的数据库中识别出结构上更相似的模板，并且SnugDock扩大了其适用性而不会丢失准确性。但是，在计算方法可以准确地对任何抗体进行建模之前，还有其他进展，包括提高CDR-H3环路建模的准确性和速度。基准测试表明，可以在更新的数据库中识别出结构上更相似的模板，并且SnugDock扩大了其适用性而不会丢失准确性。但是，在计算方法可以准确地对任何抗体进行建模之前，还有其他进展，包括提高CDR-H3环路建模的准确性和速度。基准测试表明，可以在更新的数据库中识别出结构上更相似的模板，并且SnugDock扩大了其适用性而不会丢失准确性。但是，在计算方法可以准确地对任何抗体进行建模之前，还有其他进展，包括提高CDR-H3环路建模的准确性和速度。