Are there any generalized molecular principles of thermal adaptation? Here, integrating the concepts of structural bioinformatics, sequence analysis, and classical knot theory, we develop a robust computational framework that seeks for mechanisms of thermal adaptation by comparing orthologous mesophilic-thermophilic and mesophilic-hyperthermophilic proteins of remarkable structural and topological similarities, and still leads us to context-independent results. A comprehensive analysis of 4741 high-resolution, non-redundant X-ray crystallographic structures collected from 11 hyperthermophilic, 32 thermophilic and 53 mesophilic prokaryotes unravels at least five "nearly universal" signatures of thermal adaptation, irrespective of the enormous sequence, structure, and functional diversity of the proteins compared. A careful investigation further extracts a set of amino acid changes that can potentially enhance protein thermal stability, and remarkably, these mutations are overrepresented in protein crystallization experiments, in disorder-to-order transitions and in engineered thermostable variants of existing mesophilic proteins. These results could be helpful to find a precise, global picture of thermal adaptation.

中文翻译：

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寻找蛋白质热稳定性的一般分子原理。

是否有任何广义的热适应分子原理？在这里，结合结构生物信息学，序列分析和经典结理论的概念，我们开发了一个健壮的计算框架，该研究框架通过比较具有明显结构和拓扑相似性的直系同源嗜温-嗜热和嗜温-超嗜热蛋白来寻找热适应机制。使我们获得与上下文无关的结果。从11个嗜热原核，32个嗜热原核和53个嗜温原核生物中收集到的4741个高分辨率，非冗余X射线晶体学结构的综合分析，揭示了至少5个“近乎通用”的热适应特征，无论其巨大的序列，结构和结构如何。比较蛋白质的功能多样性。仔细的研究进一步提取了一组氨基酸变化，这些变化可能潜在地增强蛋白质的热稳定性，而且值得注意的是，这些突变在蛋白质结晶实验，从无序到有序的过渡以及在现有嗜温蛋白质的工程热稳定变体中被过度表达。这些结果可能有助于找到精确的全局热适应情况。