UMR 7200 - Laboratoire d'Innovation Thérapeutique, Université de Strasbourg, Faculté de Pharmacie, 74 Route du Rhin, 67401, Illkirch, France phone: +33 3 68 85 42 21 fax: +33 3 68 85 43 10.
Mol Inform. 2017 Oct;36(10). doi: 10.1002/minf.201700042. Epub 2017 Jul 10.
Promiscuity is an interesting concept in fragment-based drug design as fragments with low specificity can be advantageous for finding many screening hits. We present a PDB-wide analysis of multi-target fragments and their binding mode conservation. Focussing on multi-target fragments, we found that the majority shows non-conserved binding modes, even if they bind in a similar conformation or similar protein targets. Surprisingly, fragment properties alone are not able to predict whether a fragment will exhibit a versatile or conserved binding mode, emphasizing the interplay between protein and fragment features during a binding event and the importance of structure-based modelling.
在基于片段的药物设计中，混杂性是一个有趣的概念，因为特异性低的片段有利于发现许多筛选命中。我们对多靶点片段及其结合模式保守性进行了全 PDB 分析。我们专注于多靶点片段，发现大多数片段显示非保守的结合模式，即使它们以相似的构象或相似的蛋白靶标结合。令人惊讶的是，仅片段特性本身不能预测片段是否会表现出多样化或保守的结合模式，这强调了在结合事件中蛋白质和片段特性之间的相互作用以及基于结构建模的重要性。
