An Interface-Driven Design Strategy Yields a Novel, Corrugated Protein Architecture,ACS Synthetic Biology

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An Interface-Driven Design Strategy Yields a Novel, Corrugated Protein Architecture
ACS Synthetic Biology ( IF 3.7 ) Pub Date : 2018-08-27 00:00:00 , DOI: 10.1021/acssynbio.8b00224
Mohammad ElGamacy ₁ , Murray Coles ₁ , Patrick Ernst ₂ , Hongbo Zhu ₁ , Marcus D. Hartmann ₁ , Andreas Plückthun ₂ , Andrei N. Lupas ₁

Affiliation

Designing proteins with novel folds remains a major challenge, as the biophysical properties of the target fold are not known a priori and no sequence profile exists to describe its features. Therefore, most computational design efforts so far have been directed toward creating proteins that recapitulate existing folds. Here we present a strategy centered upon the design of novel intramolecular interfaces that enables the construction of a target fold from a set of starting fragments. This strategy effectively reduces the amount of computational sampling necessary to achieve an optimal sequence, without compromising the level of topological control. The solenoid architecture has been a target of extensive protein design efforts, as it provides a highly modular platform of low topological complexity. However, none of the previous efforts have attempted to depart from the natural form, which is characterized by a uniformly handed superhelical architecture. Here we aimed to design a more complex platform, abolishing the superhelicity by introducing internally alternating handedness, resulting in a novel, corrugated architecture. We employed our interface-driven strategy, designing three proteins and confirming the design by solving the structure of two examples.

中文翻译：

接口驱动的设计策略产生了一种新颖的波纹蛋白结构

设计具有新颖折叠的蛋白质仍然是一项重大挑战，因为先验折叠的生物物理特性尚不清楚并且不存在描述其特征的序列图。因此，迄今为止，大多数计算设计工作都致力于创建可概括现有折叠的蛋白质。在这里，我们提出了一种基于新型分子内界面设计的策略，该界面能够从一组起始片段构建目标折叠。这种策略有效地减少了获得最佳序列所需的计算采样量，而不会影响拓扑控制的水平。螺线管体系结构一直是广泛的蛋白质设计工作的目标，因为它提供了具有低拓扑复杂性的高度模块化的平台。但是，以前的尝试都没有尝试偏离自然形态，自然形态的特征在于手形均匀的超螺旋结构。在这里，我们旨在设计一个更复杂的平台，通过引入内部交替使用的手法来消除超螺旋性，从而形成一种新颖的波纹结构。我们采用了界面驱动策略，设计了三种蛋白质，并通过解决两个例子的结构来确认设计。

更新日期：2018-08-27

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