Consistent blind protein structure generation from NMR chemical shift data
Consistent blind protein structure generation from NMR chemical shift data
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DOI：
10.1073/pnas.0800256105
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发表时间：
2008-03-25
影响因子：
11.1
通讯作者：
Bax, Ad
中科院分区：
文献类型：
--
作者：
Shen, Yang;Lange, Oliver;Bax, Ad
蛋白质 NMR 化学位移对局部结构高度敏感。描述了一个强大的协议，利用这种关系从头生成蛋白质结构，使用 C-13(α)、C-13(β)、C-13'、N-15、H-1(α) 和 H-1(N) NMR 化学位移作为输入实验参数。这些转变通常可在传统 NMR 结构测定过程的早期阶段、在结构约束的收集和分析之前获得。基于化学位移的结构测定方案使用经验优化的程序，结合标准的 ROSETTA Monte Carlo 组装和松弛方法，从蛋白质数据库中选择蛋白质片段。对大小从 56 到 129 个残基不等的 16 种蛋白质进行评估，得到了主链原子相对于实验确定的 X 射线或 NMR 结构具有 0.7-1.8 埃均方根偏差的全原子模型。该策略还以盲法成功应用于分子量高达 15.4 kDa 的 9 个蛋白质靶点，其常规 NMR 结构测定由东北结构基因组学联盟并行进行。该协议可能为高通量 NMR 结构测定提供新方向。
Protein NMR chemical shifts are highly sensitive,to local structure. A robust protocol is described that exploits this relation for de novo protein structure generation, using as input experimental parameters the C-13(alpha), C-13(beta), C-13', N-15, H-1(alpha) and H-1(N) NMR chemical shifts. These shifts are generally available at the early stage of the traditional NMR structure determination process, before the collection and analysis of structural restraints. The chemical shift based structure determination protocol uses an empirically optimized procedure to select protein fragments from the Protein Data Bank, in conjunction with the standard ROSETTA Monte Carlo assembly and relaxation methods. Evaluation of 16 proteins, varying in size from 56 to 129 residues, yielded full-atom models that have 0.7-1.8 angstrom root mean square deviations for the backbone atoms relative to the experimentally determined x-ray or NMR structures. The strategy also has been successfully applied in a blind manner to nine protein targets with molecular masses up to 15.4 kDa, whose conventional NMR structure determination was conducted in parallel by the Northeast Structural Genomics Consortium. This protocol potentially provides a new direction for high-throughput NMR structure determination.