González-Delgado Javier, Mier Pablo, Bernadó Pau, Neuvial Pierre, Cortés Juan
Université de Rennes, ENSAI, CNRS, CREST-UMR 9194, Rennes F-35000, France.
Andalusian Centre for Developmental Biology, Faculty of Experimental Sciences (Genetics Area), Universidad Pablo de Olavide, Seville 41013, Spain.
Proc Natl Acad Sci U S A. 2025 Jun 17;122(24):e2503264122. doi: 10.1073/pnas.2503264122. Epub 2025 Jun 13.
The correlation between synonymous codon usage and secondary structure in translated proteins has been widely demonstrated. This usage plays a capital role in tuning translational rates and protein folding kinetics, indirectly influencing multiple biological processes. A recent report [A. A. Rosenberg, A. Marx, A. M. Bronstein, , 2815 (2022).] suggests that the translated synonymous codon influences the [Formula: see text] dihedral angles within secondary structure elements. If true, this conclusion would have strong consequences in several scientific fields, including structural biology and protein design, where results would depend on DNA sequence rather than protein sequence. Here, we show that the original statistical methodology used in the referred study was formally incorrect. Furthermore, when using a correct approach, we demonstrate that the influence of the codon on the distribution of the dihedral angles is not statistically significant for any type of secondary structure.
同义密码子使用与翻译后蛋白质二级结构之间的相关性已得到广泛证实。这种使用在调节翻译速率和蛋白质折叠动力学方面起着重要作用，间接影响多个生物学过程。最近的一份报告[A. A. 罗森伯格、A. 马克思、A. M. 布朗斯坦， ，2815 (2022)]表明，翻译后的同义密码子会影响二级结构元件内的二面角。如果这是真的，这一结论将在包括结构生物学和蛋白质设计在内的几个科学领域产生重大影响，在这些领域中，结果将取决于DNA序列而非蛋白质序列。在这里，我们表明上述研究所使用的原始统计方法在形式上是不正确的。此外，当使用正确的方法时，我们证明密码子对二面角分布的影响对于任何类型的二级结构在统计学上都不显著。
