Exploring Structure–Activity Relationships with Three‐Dimensional Matched Molecular Pairs—A Review,ChemMedChem

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Exploring Structure–Activity Relationships with Three‐Dimensional Matched Molecular Pairs—A Review
ChemMedChem ( IF 3.6 ) Pub Date : 2018-02-09 , DOI: 10.1002/cmdc.201700628
Emanuel S. R. Ehmki ₁ , Matthias Rarey ₁

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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.

中文翻译：

探索三维匹配分子对的结构-活性关系—综述

匹配分子对（MMP）由两个仅相差几个原子的小分子组成。分子之间的微小结构差异允许对特性变化进行详细分析。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，并且必须计算叠加。额外的复杂性和不确定性，以及可用实验数据的数量较少，使模型的推导复杂化。尽管如此，仍有一些好处使过渡值得。3D概念使人们深入了解2D MMP方法经典使用的几种方法背后的机制。它可以帮助分析一系列破坏性的构效关系，或通过支架跳跃来扩展2D MMP概念。最强大的功能之一是一系列类似物之间的高置信度结构-活动关系转移。几个研究小组已经从不同的方向解决了这个问题。这些模型尤其在所使用的3D相似性度量以及所选择或设计的所应用描述符的复杂性方面有所不同。尽管如此，所有方法都通过合并3D结构信息来增加可用信息量。

更新日期：2018-02-09

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