Negative design is a group of virtual screening methods that aims at weeding out compounds with undesired properties during the early stages of drug development. These methods are mainly designed to predict three important types of pharmacological properties: drug-likeness, frequent hitters, and toxicity. In order to achieve high screening efficiency, most negative design methods are physicochemical property-based and/or substructure-based rules or filters. Such methods have advantages of simplicity and good interpretability, but they also suffer from some defects such as inflexibility, discontinuity, and hard decision-making. In this review, the advances in negative design for the evaluations of drug-likeness, frequent hitters, and toxicity are outlined. In addition, the related Web servers and software packages developed recently for negative design are summarized. Finally, future research directions in this field are discussed.

中文翻译：

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负设计在设计更理想的虚拟筛选库中的应用。

阴性设计是一组虚拟筛选方法，旨在在药物开发的早期阶段淘汰具有不良特性的化合物。这些方法的主要目的是预测三种重要的药理性质：药物相似性，频繁使用和毒性。为了实现高筛选效率，大多数负面设计方法是基于物理化学性质和/或基于子结构的规则或过滤器。此类方法具有简单性和良好的可解释性的优点，但是它们也存在一些缺陷，例如不灵活，不连续和难以决策。在这篇综述中，概述了用于评估药物相似性，频繁击中者和毒性的阴性设计的进展。此外，总结了最近为负面设计而开发的相关Web服务器和软件包。最后，讨论了该领域的未来研究方向。