Department of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia.
FEBS Lett. 2020 Jul;594(14):2199-2212. doi: 10.1002/1873-3468.13796. Epub 2020 May 9.
Nature provides a large number of functional proteins that evolved during billions of years of evolution. The diversity of natural proteins encompasses versatile functions and more than a thousand different folds, which, however, represents only a tiny fraction of all possible folds and polypeptide sequences. Recent advances in the rational design of proteins demonstrate that it is possible to design de novo protein folds unseen in nature. Novel protein topologies have been designed based on similar principles as natural proteins using advanced computational modelling or modular construction principles, such as oligomerization domains. Designed proteins exhibit several interesting features such as extreme stability, designability of 3D topologies and folding pathways. Moreover, designed protein assemblies can implement symmetry similar to the viral capsids, while, on the other hand, single-chain pseudosymmetric designs can address each position independently. Recently, the design is expanding towards the introduction of new functions into designed proteins, and we may soon be able to design molecular machines.
自然界提供了大量在数十亿年的进化过程中演变而来的功能性蛋白质。天然蛋白质的多样性包含了多种功能和一千多种不同的折叠结构，然而，这仅代表了所有可能的折叠结构和多肽序列的一小部分。最近在蛋白质的合理设计方面的进展表明，设计出自然界中从未见过的全新蛋白质折叠结构是可能的。基于与天然蛋白质相似的原理，利用先进的计算建模或模块化构建原理（如寡聚化结构域），设计出了新型蛋白质拓扑结构。设计出的蛋白质具有一些有趣的特性，如极端稳定性、3D 拓扑结构和折叠途径的可设计性。此外，设计出的蛋白质组装体可以实现类似于病毒衣壳的对称性，而另一方面，单链拟对称设计可以独立处理每个位置。最近，设计领域正在向为设计出的蛋白质引入新功能扩展，我们可能很快就能设计出分子机器。
