Bioinformatics Institute (BII), Agency for Science, Technology and Research (A⁎STAR), 30 Biopolis Street, #07-01, Matrix 138671, Singapore; Department of Biological Sciences (DBS), National University of Singapore (NUS), 8 Medical Drive, 117579, Singapore.
Curr Opin Struct Biol. 2019 Oct;58:159-165. doi: 10.1016/j.sbi.2019.06.010. Epub 2019 Jul 25.
We review studies of the protein evolution that help to formulate rules for protein design. Acknowledging the fundamental importance of Dayhoff's provision on the emergence of functional proteins from short peptides, we discuss multiple evidences of the omnipresent partitioning of protein globules into structural/functional units, using which greatly facilitates the engineering and design efforts. Closed loops and elementary functional loops, which are descendants of ancient ring-like peptides that formed fist protein domains in agreement with Dayhoff's hypothesis, can be considered as basic units of protein structure and function. We argue that future developments in protein design approaches should consider descriptors of the elementary functions, which will help to complement designed scaffolds with functional signatures and flexibility necessary for their functions.
我们回顾了有助于制定蛋白质设计规则的蛋白质进化研究。承认 Dayhoff 关于短肽中功能性蛋白质出现的规定的基本重要性，我们讨论了蛋白质球普遍划分为结构/功能单元的多种证据，这极大地促进了工程和设计工作。闭环和基本功能环，它们是古老的环形肽的后代，这些环形肽形成了拳头状的蛋白质结构域，符合 Dayhoff 的假设，可以被认为是蛋白质结构和功能的基本单元。我们认为，未来的蛋白质设计方法的发展应该考虑基本功能的描述符，这将有助于为设计支架补充功能特征和必要的灵活性，以满足其功能需求。
