Center for Bioinformatics, Universität Hamburg, Bundesstraße 43, 20146, Hamburg, Germany.
ChemMedChem. 2018 Mar 20;13(6):482-489. doi: 10.1002/cmdc.201700628. Epub 2018 Feb 9.
A matched molecular pair (MMP) consists of two small molecules that differ by a few atoms only. The minor structural difference between the molecules allows a detailed analysis of changes in properties. Three-dimensional (3D) MMPs extend the concept of chemical similarity by spatial similarity. Conformations must be generated, and superimpositions have to be calculated. The additional complexity and uncertainty as well as the smaller amount of available experimental data substantially complicates the derivation of models. Nonetheless, there are some benefits that make the transition worthwhile. The 3D concept gives detailed insight into mechanisms behind several methods classically used by the 2D MMP approach. It can help to analyze disrupted series of structure-activity relationships or extend the 2D MMP concept with scaffold hopping. One of the most powerful features is the high confidence structure-activity relationship transfer between series of analogues. Several research groups have approached the problem from different directions. The models vary especially in the 3D similarity measure used and complexity of the applied descriptor selected or designed. Nonetheless, all approaches have increased the amount of information available by incorporating 3D structural information.
配对分子对（MMP）由仅相差几个原子的两个小分子组成。分子之间的微小结构差异允许对性质变化进行详细分析。三维（3D）MMP 通过空间相似性扩展了化学相似性的概念。必须生成构象，并计算叠加。额外的复杂性和不确定性以及可用实验数据的减少大大增加了模型推导的难度。尽管如此，还是有一些好处值得进行这种转变。3D 概念深入了解了 2D MMP 方法中常用的几种方法背后的机制。它可以帮助分析结构活性关系中断的系列，或者用支架跳跃扩展 2D MMP 概念。最强大的功能之一是在类似物系列之间进行高置信度的结构活性关系转移。几个研究小组从不同的方向着手解决这个问题。这些模型的差异主要在于所使用的 3D 相似性度量和所选择或设计的应用描述符的复杂性。尽管如此，所有方法都通过包含 3D 结构信息来增加可用信息的数量。
