全新设计蛋白质的折叠机制

蛋白质全新设计和折叠研究是从两个不同的方向来理解蛋白质序列-结构-功能关系这一结构生物学重要问题. 蛋白质全新设计取得的成功实例一定程度上检验了人们对蛋白质结构和相互作用理解的准确性, 但它们中多数所表现的不同于天然蛋白质的折叠动力学特征也表明, 要达到最终的功能化实现目标还面临着不少的挑战. 本文综述了蛋白质全新设计的发展过程及现状, 蛋白质折叠研究在实验、理论及模拟方面的研究进展, 以及全新设计蛋白质的折叠机制的研究现状. 阐述了深入了解全新设计蛋白质与天然蛋白质折叠机制的不同, 可以为进一步有效地合理化设计蛋白质提供有益的参考.

Folding Mechanism of De novo Designed Proteins

Protein de novo design and protein folding are two different means to investigate“sequencestructure- function”relationship of proteins, which is one of the most important focuses in structural biology. The successful achievements in protein de novo design indicate the understanding accuracy of the knowledge in protein structure and interaction, while most of those designed proteins show different folding kinetic features from nature occurring proteins, which implies that there are still many challenges to the aim of getting them to play expected biological function. In this review, the status of research and development for protein de novo design, as well as the study progress of protein folding in experimental, theoretical and simulation aspects, have been introduced. Further, the investigations of folding mechanism of de novo designed proteins have been reviewed, and the new clue has been proposed that systematically investigation of the essence of different folding mechanism between the two types of protein would help to provide useful insight for more efficient protein rotational design.