In silico peptide-directed ligand design complements experimental peptide-directed binding for protein-protein interaction modulator discovery.
In silico peptide-directed ligand design complements experimental peptide-directed binding for protein-protein interaction modulator discovery.
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DOI：
10.1039/d0cb00148a
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发表时间：
2021-02-01
影响因子：
4.1
通讯作者：
Beekman AM
中科院分区：
文献类型：
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作者：
Howell LA;Beekman AM
利用Mcl-1/Noxa的蛋白质-蛋白质相互作用，直接比较了两种有效的调节剂发现方法。在电脑肽定向配体设计进行了评价实验肽定向结合，允许发现两个新的抑制剂Mcl-1/Noxa与细胞活性。计算机模拟肽定向配体设计显示体外命中率为80%（IC 50 < 100 μM）。这两种快速有效的方法为蛋白质-蛋白质相互作用调节剂的发现提供了互补的功能。利用Mcl-1/Noxa的蛋白质-蛋白质相互作用，直接比较了两种有效的调节剂发现方法。
Using the protein–protein interaction of Mcl-1/Noxa, two methods for efficient modulator discovery are directly compared. In silico peptide-directed ligand design is evaluated against experimental peptide-directed binding, allowing for the discovery of two new inhibitors of Mcl-1/Noxa with cellular activity. In silico peptide-directed ligand design demonstrates an in vitro hit rate of 80% (IC50 < 100 μM). The two rapid and efficient methods demonstrate complementary features for protein–protein interaction modulator discovery. Using the protein–protein interaction of Mcl-1/Noxa, two methods for efficient modulator discovery are directly compared.