Design of a novel globular protein fold with atomic-level accuracy
Design of a novel globular protein fold with atomic-level accuracy
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DOI：
10.1126/science.1089427
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发表时间：
2003-11-21
期刊：
影响因子：
56.9
通讯作者：
Baker, D
中科院分区：
文献类型：
--
作者：
Kuhlman, B;Dantas, G;Baker, D
计算蛋白质设计的一个主要挑战是创建具有任意选择的三维结构的新型蛋白质。在这里，我们使用了在序列设计和结构预测之间迭代的通用计算策略，设计了一种具有新颖序列和拓扑结构的名为 Top7 的 93 个残基 α/β 蛋白。实验发现Top7是折叠的并且极其稳定，并且Top7的X射线晶体结构与设计模型相似（均方根偏差等于1.2埃）。设计新的蛋白质折叠的能力使得探索自然界中尚未观察到的蛋白质宇宙的大片区域成为可能。
A major challenge of computational protein design is the creation of novel proteins with arbitrarily chosen three-dimensional structures. Here, we used a general computational strategy that iterates between sequence design and structure prediction to design a 93-residue alpha/beta protein called Top7 with a novel sequence and topology. Top7 was found experimentally to be folded and extremely stable, and the x-ray crystal structure of Top7 is similar (root mean square deviation equals 1.2 angstroms) to the design model. The ability to design a new protein fold makes possible the exploration of the large regions of the protein universe not yet observed in nature.