We describe the computational design of proteins that bind the potent analgesic fentanyl. Our approach employs a fast docking algorithm to find shape complementary ligand placement in protein scaffolds, followed by design of the surrounding residues to optimize binding affinity. Co-crystal structures of the highest affinity binder reveal a highly preorganized binding site, and an overall architecture and ligand placement in close agreement with the design model. We use the designs to generate plant sensors for fentanyl by coupling ligand binding to design stability. The method should be generally useful for detecting toxic hydrophobic compounds in the environment.

中文翻译：

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强效阿片类芬太尼环境传感器的计算设计

我们描述了结合强效镇痛芬太尼的蛋白质的计算设计。我们的方法采用快速对接算法来找到蛋白质支架中形状互补的配体位置，然后设计周围的残基以优化结合亲和力。最高亲和力结合剂的共晶结构揭示了高度预先组织的结合位点，以及与设计模型非常一致的整体结构和配体位置。我们使用这些设计通过将配体结合与设计稳定性耦合来生成芬太尼的植物传感器。该方法通常可用于检测环境中的有毒疏水化合物。