Astex Pharmaceuticals,436 Cambridge Science Park, Milton Road, Cambridge, CB4 0QA, UK.
Astex Pharmaceuticals,436 Cambridge Science Park, Milton Road, Cambridge, CB4 0QA, UK.
Drug Discov Today. 2019 May;24(5):1081-1086. doi: 10.1016/j.drudis.2019.03.009. Epub 2019 Mar 14.
We present a novel crystallographic screening methodology (MiniFrags) that employs high-concentration aqueous soaks with a chemically diverse and ultra-low-molecular-weight library (heavy atom count 5-7) to identify ligand-binding hot and warm spots on proteins. We propose that MiniFrag screening represents a highly effective method for guiding optimisation of fragment-derived lead compounds or chemical tools and that the high screening hit rates reflect enhanced sampling of chemical space.
我们提出了一种新颖的晶体筛选方法（MiniFrags），该方法采用高浓度的水浸泡，结合化学多样性和超低分子量文库（重原子数 5-7），以确定蛋白质上的配体结合热点和温点。我们认为，MiniFrag 筛选代表了一种非常有效的方法，可以指导片段衍生的先导化合物或化学工具的优化，而高筛选命中率反映了化学空间的增强采样。
