De novo protein design: Fully automated sequence selection
De novo protein design: Fully automated sequence selection
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DOI：
10.1126/science.278.5335.82
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发表时间：
1997-10-03
期刊：
影响因子：
56.9
通讯作者：
Mayo, SL
中科院分区：
文献类型：
--
作者：
Dahiyat, BI;Mayo, SL
描述了整个蛋白质的新序列的第一个全自动设计和实验验证。基于物理化学势函数和立体化学约束的计算设计算法用于筛选1.9 x 10（27）可能的氨基酸序列的组合库，以与设计目标兼容，该目标是基于多肽基链链链链链链链链链链链蛋白基序的兼容性锌指域。 BLAST搜索表明，设计的序列完整序列设计1（FSD-1）对任何已知的蛋白质序列具有非常低的身份。 FSD-1的溶液结构通过核磁共振光谱求解，并表明FSD-1形成紧凑的井井有条结构，这与设计目标结构非常吻合，该结果表明计算方法可以执行巨大的组合性组合。蛋白质设计所需的搜索，这表明可以在各种结构环境中使用一种公正和定量算法。
The first fully automated design and experimental validation of a novel sequence for an entire protein is described. A computational design algorithm based on physical chemical potential functions and stereochemical constraints was used to screen a combinatorial library of 1.9 x 10(27) possible amino acid sequences for compatibility with the design target, a beta beta alpha protein motif based on the polypeptide backbone structure of a zinc finger domain. A BLAST search shows that the designed sequence, full sequence design 1 (FSD-1), has very low identity to any known protein sequence. The solution structure of FSD-1 was solved by nuclear magnetic resonance spectroscopy and indicates that FSD-1 forms a compact well-ordered structure, which is in excellent agreement with the design target structure, This result demonstrates that computational methods can perform the immense combinatorial search required for protein design, and it suggests that an unbiased and quantitative algorithm can be used in various structural contexts.