School of Natural Sciences, University of Tasmania, Private Bag 37, Hobart, Tasmania, 7001, Australia.
Biol Rev Camb Philos Soc. 2023 Feb;98(1):243-262. doi: 10.1111/brv.12905. Epub 2022 Oct 9.
Proteins form arguably the most significant link between genotype and phenotype. Understanding the relationship between protein sequence and structure, and applying this knowledge to predict function, is difficult. One way to investigate these relationships is by considering the space of protein folds and how one might move from fold to fold through similarity, or potential evolutionary relationships. The many individual characterisations of fold space presented in the literature can tell us a lot about how well the current Protein Data Bank represents protein fold space, how convergence and divergence may affect protein evolution, how proteins affect the whole of which they are part, and how proteins themselves function. A synthesis of these different approaches and viewpoints seems the most likely way to further our knowledge of protein structure evolution and thus, facilitate improved protein structure design and prediction.
蛋白质可以说是基因型和表型之间最重要的联系。理解蛋白质序列和结构之间的关系,并将这方面的知识应用于预测功能,是很困难的。一种研究这些关系的方法是考虑蛋白质折叠的空间,以及如何通过相似性或潜在的进化关系从一种折叠转移到另一种折叠。文献中提出的许多关于折叠空间的个体特征,可以告诉我们当前的蛋白质数据库(PDB)对蛋白质折叠空间的代表性如何,收敛和发散如何影响蛋白质进化,蛋白质如何影响它们所属的整体,以及蛋白质本身如何发挥作用。综合这些不同的方法和观点,似乎是进一步了解蛋白质结构进化的最有可能的途径,从而有助于改进蛋白质结构设计和预测。