Kenny Peter W
Berwick-on-Sea, North Coast Road, Blanchisseuse, Saint George, Trinidad and Tobago.
J Cheminform. 2019 Jan 31;11(1):8. doi: 10.1186/s13321-019-0330-2.
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.
配体效率是药物研发中广泛使用的设计参数。它通过将亲和力按分子大小进行缩放来计算，并且对用于表达亲和力的浓度单位有着复杂的依赖性，这种依赖性源于对数函数无法处理有量纲的参数。因此，对效率的认知会因浓度单位的选择而有所不同，有人认为配体效率指标没有物理意义，也不应被视为一种度量标准。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，并通过片段到先导物的优化进行了说明。还从物理化学角度详细研究了基团效率和拟合质量。在整个研究过程中都强调了直接研究亲和力与分子大小之间关系的重要性，并提出了一种替代配体效率的方法，用于将亲和力相对于分子大小进行归一化。
