Intrinsically disordered proteins or intrinsically disordered regions (IDPs or IDRs) are those that do not fold into defined tertiary structures under physiological conditions. Given their prevalence in various diseases, IDPs are attractive therapeutic targets. However, because of the dynamic nature of the IDP structure, conventional structure-based drug design methods cannot be directly applied. Thanks to recent progress in understanding the mechanisms underlying IDP and ligand interactions, computational strategies for IDP-targeted rational drug discovery are emerging. Here, we summarize recent developments in computational IDP drug design strategies and their successful applications, analyze the typical properties of reported IDP-binding compounds (iIDPs), and discuss the major challenges ahead as well as possible solutions.

内在无序的蛋白质或内在无序的区域（IDP或IDR）是在生理条件下不会折叠成确定的三级结构的蛋白质或内在无序的区域。鉴于其在各种疾病中的流行，IDP是有吸引力的治疗靶标。然而，由于IDP结构的动态性质，常规的基于结构的药物设计方法不能直接应用。由于最近在理解IDP和配体相互作用的机理方面取得了进展，因此出现了以IDP为目标的合理药物发现的计算策略。在这里，我们总结了计算性IDP药物设计策略及其成功应用的最新进展，分析了已报道的IDP结合化合物（iIDP）的典型特性，并讨论了未来的主要挑战以及可能的解决方案。