Design of structurally distinct proteins using strategies inspired by evolution.
Design of structurally distinct proteins using strategies inspired by evolution.
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DOI：
10.1126/science.aad8036
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发表时间：
2016-05-06
期刊：
影响因子：
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通讯作者：
Kuhlman B
中科院分区：
文献类型：
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作者：
Jacobs TM;Williams B;Williams T;Xu X;Eletsky A;Federizon JF;Szyperski T;Kuhlman B
自然重组将预先存在的蛋白质片段组合在一起，以创建新的三级结构和功能。我们描述了一种称为SEWING的计算协议，它受到这个过程的启发，并从现有结构的连接或断开片段中构建新的蛋白质。使用SEWING设计的螺旋蛋白质含有其他从头设计的蛋白质所不具有的结构特征，并且在某些情况下保持折叠至超过100 °C。设计的蛋白质CA 01和DA 05 R1的高分辨结构分别用X射线晶体学（2.2 μ m分辨率）和NMR解析，与设计模型吻合良好。这种方法提供了一种新的策略，以快速创建大量的多样化和可设计的蛋白质支架。
Natural recombination combines pieces of pre-existing proteins to create new tertiary structures and functions. We describe a computational protocol, called SEWING, which is inspired by this process and builds new proteins from connected or disconnected pieces of existing structures. Helical proteins designed with SEWING contain structural features absent from other de novo designed proteins and in some cases remain folded to over 100 °C. High resolution structures of the designed proteins CA01 and DA05R1 were solved by X-ray crystallography (2.2 Å resolution) and NMR respectively, and there was excellent agreement with the design models. This method provides a new strategy to rapidly create large numbers of diverse and designable protein scaffolds.