Ferrando Juan, Solomon Lee A
Department of Biology, George Mason University, 4400 University Dr, Fairfax, VA 22030, USA.
Department of Chemistry and Biochemistry, George Mason University, 10920 George Mason Circle, Manassas, VA 20110, USA.
Life (Basel). 2021 Mar 10;11(3):225. doi: 10.3390/life11030225.
De novo protein design is a powerful methodology used to study natural functions in an artificial-protein context. Since its inception, it has been used to reproduce a plethora of reactions and uncover biophysical principles that are often difficult to extract from direct studies of natural proteins. Natural proteins are capable of assuming a variety of different structures and subsequently binding ligands at impressively high levels of both specificity and affinity. Here, we will review recent examples of de novo design studies on binding reactions for small molecules, nucleic acids, and the formation of protein-protein interactions. We will then discuss some new structural advances in the field. Finally, we will discuss some advancements in computational modeling and design approaches and provide an overview of some modern algorithmic tools being used to design these proteins.
从头蛋白质设计是一种强大的方法，用于在人工蛋白质环境中研究自然功能。自其诞生以来，它已被用于重现大量反应，并揭示通常难以从天然蛋白质的直接研究中提取的生物物理原理。天然蛋白质能够呈现多种不同的结构，随后以令人印象深刻的高特异性和亲和力水平结合配体。在这里，我们将回顾关于小分子、核酸结合反应以及蛋白质-蛋白质相互作用形成的从头设计研究的近期实例。然后，我们将讨论该领域的一些新的结构进展。最后，我们将讨论计算建模和设计方法的一些进展，并概述一些用于设计这些蛋白质的现代算法工具。
