3D pharmacophore models are three‐dimensional ensembles of chemically defined interactions of a ligand in its bioactive conformation. They represent an elegant way to decipher chemically encoded ligand information and have therefore become a valuable tool in drug design. In this review, we provide an overview on the basic concept of this method and summarize key studies for applying 3D pharmacophore models in virtual screening and mechanistic studies for protein functionality. Moreover, we discuss recent developments in the field. The combination of 3D pharmacophore models with molecular dynamics simulations could be a quantum leap forward since these approaches consider macromolecule–ligand interactions as dynamic and therefore show a physiologically relevant interaction pattern. Other trends include the efficient usage of 3D pharmacophore information in machine learning and artificial intelligence applications or freely accessible web servers for 3D pharmacophore modeling. The recent developments show that 3D pharmacophore modeling is a vibrant field with various applications in drug discovery and beyond.

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下一代3D药效团建模

3D药效团模型是配体在其生物活性构象上化学定义的相互作用的三维整体。它们代表了一种解密化学编码配体信息的绝妙方法，因此已成为药物设计中的宝贵工具。在本文中，我们概述了该方法的基本概念，并总结了在蛋白质功能的虚拟筛选和机理研究中应用3D药效团模型的关键研究。此外，我们讨论了该领域的最新发展。3D药效团模型与分子动力学模拟的结合可能是一个巨大的飞跃，因为这些方法将大分子-配体相互作用视为动态的，因此显示出生理上相关的相互作用模式。其他趋势包括在机器学习和人工智能应用程序中有效使用3D药效团信息，或用于3D药效团建模的可自由访问的Web服务器。最近的发展表明，3D药效团建模是一个生机勃勃的领域，在药物发现及以后的研究中具有各种应用。