PROTAC virtual screening: A retrospective screening exercise

My goal is to test whether retrospective virtual screening approaches can guide the design of PROTACs. As a first step, I showed that HADDOCK was the best protein-protein docking tool among those I tested to predict how E3 ligases interact with their protein substrates. Here, I ask whether docking virtual libraries of PROTAC candidates to these E3 ligase – substrate protein interfaces can be used to predict which PROTACs are active.

本研究旨在验证回顾性虚拟筛选（retrospective virtual screening）策略能否指导蛋白降解靶向嵌合体（PROTACs）的设计。作为研究的第一步，本研究证实，在本次测试的多款工具中，HADDOCK是预测E3连接酶（E3 ligases）与其蛋白底物（protein substrates）相互作用的最优蛋白-蛋白对接工具。本研究进一步探讨：将PROTAC候选化合物虚拟库与上述E3连接酶-底物蛋白结合界面进行分子对接，是否可用于预测具有活性的PROTACs。