High-resolution protein design with backbone freedom
High-resolution protein design with backbone freedom
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DOI：
10.1126/science.282.5393.1462
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发表时间：
1998-11-20
期刊：
影响因子：
56.9
通讯作者：
Kim, PS
中科院分区：
文献类型：
--
作者：
Harbury, PB;Plecs, JJ;Kim, PS
计算技术的最新进展使得能够设计具有预定的、天然存在的主链结构的蛋白质中的精确侧链包装。由于这些方法没有模拟蛋白质主链的灵活性，因此它们缺乏探索新主链构象的广度。这里描述了具有右旋超螺旋扭曲的螺旋束蛋白家族的从头设计。在设计中，整体蛋白质折叠是通过疏水极性残基模式指定的，而束寡聚状态、详细的主链构象和内部侧链旋转异构体是通过交替主链结构中包装的计算计数来设计的。主链的灵活性是通过主链的代数参数化来实现的。设计的肽根据设计目标形成ct螺旋二聚体、三聚体和四聚体。四聚体的晶体结构在原子细节上与设计的结构相匹配。
Recent advances in computational techniques have allowed the design of precise side-chain packing in proteins with predetermined, naturally occurring backbone structures. Because these methods do not model protein main-chain flexibility, they lack the breadth to explore novel backbone conformations. Here the de novo design of a family of or-helical bundle proteins with a right-handed superhelical twist is described. In the design, the overall protein fold was specified by hydrophobic-polar residue patterning, whereas the bundle oligomerization state, detailed main-chain conformation, and interior side-chain rotamers were engineered by computational enumerations of packing in alternate backbone structures. Main-chain flexibility was incorporated through an algebraic parameterization of the backbone. The designed peptides form ct-helical dimers, trimers, and tetramers in accord with the design goals. The crystal structure of the tetramer matches the designed structure in atomic detail.