Tripos, Inc., 2935 East Rodeo Park Drive, Santa Fe, NM 87505, USA.
Expert Opin Drug Discov. 2006 Sep;1(4):311-21. doi: 10.1517/17460441.1.4.311.
Structural novelty has depended for its discovery on a combination of experimental and virtual screening, where virtual screening has meant either docking into a receptor or pharmacophoric or two-dimensional similarity. In this review, leadhopping denotes a new, far more convenient and apparently quite as effective, set of virtual screening methods, all of which emphasise a much more detailed similarity in ligand shape than the pharmacophore approach. Furthermore, some of these leadhopping methods have been adapted to address much broader needs, such as accelerated and simplified lead optimisation, access to an unprecedented vast structural space, and even useful forecasts of off-target pharmacological effects in humans. These methods seem robust and automatable enough to be used directly by laboratory chemists.
结构新颖性的发现依赖于实验和虚拟筛选的结合，其中虚拟筛选意味着要么对接受体，要么基于药效基团或二维相似性。在这篇综述中，leadhopping 表示一套新的、更方便、显然同样有效的虚拟筛选方法，这些方法都强调配体形状的更详细相似性，而不是药效基团方法。此外，这些 leadhopping 方法中的一些已经被改编，以满足更广泛的需求，如加速和简化先导化合物优化，获得前所未有的广阔结构空间，甚至对人类中潜在的非靶标药理作用进行有用的预测。这些方法似乎足够稳健和自动化，可以直接由实验室化学家使用。
