Virtual screening for high affinity guests for synthetic supramolecular receptors.
Virtual screening for high affinity guests for synthetic supramolecular receptors.
复制标题
DOI：
10.1039/c5sc00534e
复制
发表时间：
2015-05-01
期刊：
影响因子：
8.4
通讯作者：
Ward MD
中科院分区：
文献类型：
--
作者：
Cullen W;Turega S;Hunter CA;Ward MD
蛋白质/配体对接程序“GOLD”可用于识别合成配位笼宿主的新的强结合客人。最初为药物发现开发的蛋白质/配体对接软件GOLD已用于虚拟屏幕中，以识别在水中立方配位笼的空腔中以极高亲和力（K = 107 M-1）结合的小分子。使用已知的客体作为训练集开发了评分函数，并通过引入额外的项来修改，以考虑客体结合时的灵活性损失。然后在GOLD中使用该评分函数，成功地识别了15个新的客体，并准确地预测了结合常数。这种方法为虚拟筛选大型化合物库以识别合成宿主的新客体提供了强大的预测工具，从而通过消除对实验试错的依赖来大大简化和加速识别客体的过程。
The protein/ligand docking programme ‘GOLD’ can be used to identify new strongly-binding guests for a synthetic coordination cage host. The protein/ligand docking software GOLD, which was originally developed for drug discovery, has been used in a virtual screen to identify small molecules that bind with extremely high affinities (K ≈ 107 M–1) in the cavity of a cubic coordination cage in water. A scoring function was developed using known guests as a training set and modified by introducing an additional term to take account of loss of guest flexibility on binding. This scoring function was then used in GOLD to successfully identify 15 new guests and accurately predict the binding constants. This approach provides a powerful predictive tool for virtual screening of large compound libraries to identify new guests for synthetic hosts, thereby greatly simplifying and accelerating the process of identifying guests by removing the reliance on experimental trial-and-error.