Barbosa Frédérique, Horvath Dragos
CEREP, 128, rue Danton, 92506 Rueil Malmaison, France.
Curr Top Med Chem. 2004;4(6):589-600. doi: 10.2174/1568026043451186.
This paper reviews the main efforts undertaken up to date in order to understand, rationalize and apply the similarity principle (similar compounds=>similar properties) as a computational tool in modern drug discovery. The best suited mathematical expression of this classical working hypothesis of medicinal chemistry needs to be carefully chosen (out of the virtually infinite possible implementations in terms of molecular descriptors and molecular similarity metrics), in order to achieve an optimal validation of the hypothesis that molecules that are neighbors in the Structural Space will also display similar properties. This overview will show why no single "absolute" measure of molecular similarity can be conceived, and why molecular similarity scores should be considered tunable tools that need to be adapted to each problem to solve.
本文回顾了迄今为止为理解、合理化并应用相似性原则（相似化合物 => 相似性质）作为现代药物发现中的一种计算工具所做的主要工作。为了实现对“结构空间中相邻的分子也将表现出相似性质”这一假设的最佳验证，需要仔细选择（从分子描述符和分子相似性度量方面几乎无限可能的实现方式中）这种药物化学经典工作假设的最合适数学表达式。本综述将说明为什么无法设想单一的“绝对”分子相似性度量，以及为什么分子相似性分数应被视为需要针对每个待解决问题进行调整的可调工具。
