Design of structurally distinct proteins using strategies inspired by evolution

被引：108

作者：

Jacobs, T. M. ^{[1
]}

Williams, B. ^{[2
]}

Williams, T. ^{[2
]}

Xu, X. ^{[3
,4
]}

Eletsky, A. ^{[3
,4
]}

Federizon, J. F. ^{[3
]}

Szyperski, T. ^{[3
]}

Kuhlman, B. ^{[2
,5
]}

机构：

[1] Univ N Carolina, Program Bioinformat & Computat Biol, Chapel Hill, NC 27599 USA

[2] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA

[3] SUNY Buffalo, Dept Chem, Buffalo, NY 14260 USA

[4] Univ N Carolina, Northeast Struct Genom Consortium, Chapel Hill, NC 27599 USA

[5] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

来源：

SCIENCE | 2016年 / 352卷 / 6286期

关键词：

RATIONAL DESIGN; CONSERVATION; COMBINATION; DOMAIN; FOLD;

D O I：

10.1126/science.aad8036

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Natural recombination combines pieces of preexisting 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 at more than 100C. High-resolution structures of the designed proteins CA01 and DA05R1 were solved by x-ray crystallography (2.2 angstrom resolution) and nuclear magnetic resonance, 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.

引用

页码：687 / 690

页数：4

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