Ligand efficiency is a widely used design parameter in drug discovery. It is calculated by scaling affinity by molecular size and has a nontrivial dependency on the concentration unit used to express affinity that stems from the inability of the logarithm function to take dimensioned arguments. Consequently, perception of efficiency varies with the choice of concentration unit and it is argued that the ligand efficiency metric is not physically meaningful nor should it be considered to be a metric. The dependence of ligand efficiency on the concentration unit can be eliminated by defining efficiency in terms of sensitivity of affinity to molecular size and this is illustrated with reference to fragment-to-lead optimizations. Group efficiency and fit quality are also examined in detail from a physicochemical perspective. The importance of examining relationships between affinity and molecular size directly is stressed throughout this study and an alternative to ligand efficiency for normalization of affinity with respect to molecular size is presented.

中文翻译：

---

配体效率的性质。

配体效率是药物发现中广泛使用的设计参数。它是通过按分子大小缩放亲和力来计算的，并且对用于表达亲和力的浓度单位具有非平凡的依赖性，这是由于对数函数无法采用已确定尺寸的参数所致。因此，对效率的认识随浓度单位的选择而变化，并且认为配体效率度量在物理上没有意义，也不应被视为度量。通过根据亲和力对分子大小的敏感性来定义效率，可以消除配体效率对浓度单位的依赖性，这可以参考片段到最优化来说明。还从理化角度详细检查了小组效率和配合质量。