Mason J S, Good A C, Martin E J
Structural Biology and Modeling, Bristol-Myers Squibb, P.O. Box 4000, Princeton, NJ 08543, USA.
Curr Pharm Des. 2001 May;7(7):567-97. doi: 10.2174/1381612013397843.
In this chapter we review the use of 3-D pharmacophores in drug discovery. Recent advances are highlighted, including the application of pharmacophore descriptors generated both from ligands and protein binding sites. The application of 3-D pharmacophore fingerprints as molecular descriptors for similarity and diversity applications such as virtual screening, library design and QSAR is discussed. In addition, we highlight the quantification of structure-based diversity using site-derived fingerprints, and review virtual screening methods using both single refined hypotheses and the fingerprints of multiple potential hypotheses. Further, we discuss methods that take protein flexibility and molecular shape-into account. Each of the above techniques are reviewed with particular reference to the recent advances, advantages and challenges of each methodology.
在本章中，我们回顾了三维药效团在药物发现中的应用。重点介绍了近期的进展，包括从配体和蛋白质结合位点生成的药效团描述符的应用。讨论了三维药效团指纹作为分子描述符在虚拟筛选、库设计和定量构效关系等相似性和多样性应用中的应用。此外，我们强调了使用位点衍生指纹对基于结构的多样性进行量化，并回顾了使用单一优化假设和多个潜在假设指纹的虚拟筛选方法。此外，我们还讨论了考虑蛋白质灵活性和分子形状的方法。以上每种技术都结合每种方法的最新进展、优点和挑战进行了回顾。
