Aromatic rings are important residues for biological interactions and appear to a large extent as part of protein–drug and protein–protein interactions. They are relevant for both protein stability and molecular recognition processes due to their natural occurrence in aromatic aminoacids (Trp, Phe, Tyr and His) as well as in designed drugs since they are believed to contribute to optimizing both affinity and specificity of drug-like molecules. Despite the mentioned relevance, the impact of aromatic clusters on protein–protein and protein–drug complexes is still poorly characterized, especially in those that go beyond a dimer. In this work, we studied protein–drug and protein–protein complexes and systematically analyzed the presence and structure of their aromatic clusters. Our results show that aromatic clusters are highly prevalent in both protein–protein and protein–drug complexes, and suggest that protein–protein aromatic clusters have idealized interactions, probably because they were optimized by evolution, as compared to protein–drug clusters that were manually designed. Interestingly, the configuration, solvent accessibility and secondary structure of aromatic residues in protein–drug complexes shed light on the relation between these properties and compound affinity, allowing researchers to better design new molecules.

中文翻译：

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蛋白质-蛋白质和蛋白质-药物复合物中的芳香族簇


芳香环是生物相互作用的重要残基，在很大程度上是蛋白质-药物和蛋白质-蛋白质相互作用的一部分。由于它们天然存在于芳香族氨基酸（色氨酸、苯丙氨酸、酪氨酸和组氨酸）以及设计药物中，因此它们与蛋白质稳定性和分子识别过程相关，因为它们被认为有助于优化类药物的亲和力和特异性。分子。尽管提到了相关性，但芳香族簇对蛋白质-蛋白质和蛋白质-药物复合物的影响仍然知之甚少，特别是在二聚体以外的复合物中。在这项工作中，我们研究了蛋白质-药物和蛋白质-蛋白质复合物，并系统分析了它们芳香族簇的存在和结构。我们的结果表明，芳香族簇在蛋白质-蛋白质和蛋白质-药物复合物中都非常普遍，并且表明蛋白质-蛋白质芳香族簇具有理想化的相互作用，可能是因为与人工合成的蛋白质-药物簇相比，它们通过进化得到了优化。设计的。有趣的是，蛋白质-药物复合物中芳香族残基的构型、溶剂可及性和二级结构揭示了这些特性和化合物亲和力之间的关系，使研究人员能够更好地设计新分子。