Essentials of de novo protein design: Methods and applications,Wiley Interdisciplinary Reviews: Computational Molecular Science

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Essentials of de novo protein design: Methods and applications
Wiley Interdisciplinary Reviews: Computational Molecular Science ( IF 16.8 ) Pub Date : 2018-07-17 , DOI: 10.1002/wcms.1374
Enrique Marcos ₁ , Daniel-Adriano Silva _{2,

3}

Affiliation

The field of de novo protein design has undergone a rapid transformation in the last decade and now enables the accurate design of protein structures with exceptional stability and in a large variety of folds not necessarily restricted to those seen in nature. Before the existence of de novo protein design, traditional strategies to engineer proteins relied exclusively on modifying existing proteins already with a similar to desired function or, at least, a suitable geometry and enough stability to tolerate mutations needed for incorporating the desired functions. De novo computational protein design, instead, allows to completely overcome this limitation by permitting the access to a virtually infinite number of protein shapes that can be suitable candidates to engineer function. Recently, we have seen the first examples of such functionalization in the form of de novo proteins custom designed to bind specific targets or small molecules with novel medical and biotechnological applications. Despite this progress, the incursion on this nascent field can be difficult due to the plethora of approaches available and their constant evolution. Here, we review the most relevant computational methods for de novo protein design with the aim of compiling a comprehensive guide for researchers embarking on this field. We illustrate most of the concepts in the view of Rosetta, which is the most extensively developed software for de novo protein design, but we highlight relevant work with other protein modeling softwares. Finally, we give an overall view of the current challenges and future opportunities in the field.

中文翻译：

从头蛋白质设计的要点：方法和应用

领域从头蛋白质设计经历了在过去十年中迅速转变，现在使蛋白质结构与优异的稳定性和种类繁多的褶皱不一定仅限于那些在自然界中看到的精确的设计。在存在从头蛋白质设计之前，工程化蛋白质的传统策略仅依赖于修饰已经具有与所需功能相似或至少具有合适的几何结构和足够稳定性的现有蛋白质，以容许掺入所需功能的突变。从头开始相反，计算机蛋白质设计允许通过访问几乎无限数量的蛋白质形状来完全克服此限制，这些蛋白质形状可以作为工程功能的合适候选对象。最近，我们已经看到了从头蛋白形式定制化的这种功能化的第一个例子，这些蛋白被定制为结合新的医学和生物技术应用结合特定的靶标或小分子。尽管取得了这些进展，但由于有大量可用的方法及其不断发展，因此入侵这一新生领域仍然很困难。在这里，我们回顾了从头开始最相关的计算方法蛋白质设计的目的是为从事该领域的研究人员编写一份综合指南。我们从Rosetta（它是从头进行蛋白质设计的最广泛开发的软件）的观点说明了大多数概念，但是我们重点介绍了与其他蛋白质建模软件的相关工作。最后，我们给出了该领域当前的挑战和未来机会的总体看法。

更新日期：2018-07-17

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