Protein NMR structure determination with automated NOE assignment using the new software CANDID and the torsion angle dynamics algorithm DYANA
Protein NMR structure determination with automated NOE assignment using the new software CANDID and the torsion angle dynamics algorithm DYANA
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DOI：
10.1016/s0022-2836(02)00241-3
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发表时间：
2002-05-24
影响因子：
5.6
通讯作者：
Wüthrich, K
中科院分区：
文献类型：
--
作者：
Herrmann, T;Güntert, P;Wüthrich, K
结合自动NOE分配和结构测定模块（CANDID）是一个新的软件，用于高效的NMR结构测定的NOESY谱的自动分配的蛋白质。CANDID使用迭代方法，使用快速DYANA扭转角动力学算法进行NOE交叉峰分配和蛋白质结构计算的多个循环，使得每个CANDID循环的结果包括所有可用光谱中的详尽的、可能模糊的NOE交叉峰分配和由一束构象异构体表示的三维蛋白质结构。第一个CANDID循环的输入包括氨基酸序列、来自序列特异性共振分配的化学位移列表以及一个或多个二维、三维或四维NOESY光谱中的交叉峰位置和体积列表。除了用于第一循环的完整输入之外，第二和后续CANDID循环的输入还包含来自前一循环的三维蛋白质结构。CANDID包括两个新的元素，使其相对于输入数据中的伪影的存在具有鲁棒性，即网络锚定和约束组合，其在从头蛋白质结构确定中具有关键作用，用于通过第一个CANDID循环成功生成正确的多肽折叠。网络锚定利用以下事实：任何正确NOE交叉峰分配的网络形成自洽集合;因此，每个单独NOE交叉峰的初始基于化学位移的分配通过它们可以嵌入到由所有其他NOE交叉峰分配形成的网络中的程度来加权。约束组合通过将两个或几个峰的分配组合到单个上限距离约束中来减少蛋白质结构计算的输入中的伪影NOE上限距离约束的有害影响，这降低了伪影峰的存在将影响结构计算的结果的概率。CANDID测试计算是用四种蛋白质的NMR数据集进行的，这些蛋白质的高质量结构先前已经通过交互式协议解决，并且它们在剩余约束违反以及原子坐标的精度和准确性方面产生了与这些参考结构测定相当的结果。CANDID方法已通过另外四种蛋白质的从头NMR结构测定进一步验证。在这些计算中获得的经验表明，一旦几乎完整的序列特异性共振分配是可用的，自动CANDID方法的结果大大提高了效率的NOESY光谱分析。事实上，正确的折叠是在循环I的一个tic novo结构计算是一个最重要的进步，实现与CANDID相比，以前提出的自动NOESY分配方法，不使用网络锚定和约束组合。(C)2002爱思唯尔科技有限公司版权所有。
Combined automated NOE assignment and structure determination module (CANDID) is a new software for efficient NMR structure determination of proteins by automated assignment of the NOESY spectra. CANDID uses an iterative approach with multiple cycles of NOE crosspeak assignment and protein structure calculation using the fast DYANA torsion angle dynamics algorithm, so that the result from each CANDID cycle consists of exhaustive, possibly ambiguous NOE cross-peak assignments in all available spectra and a three-dimensional protein structure represented by a bundle of conformers. The input for the first CANDID cycle consists of the amino acid sequence, the chemical shift list from the sequence-specific resonance assignment, and listings of the cross-peak positions and volumes in one or several two, three or four-dimensional NOESY spectra. The input for the second and subsequent CANDID cycles contains the three-dimensional protein structure from the previous cycle, in addition to the complete input used for the first cycle. CANDID includes two new elements that make it robust with respect to the presence of artifacts in the input data, i.e. network-anchoring and constraint-combination, which have a key role in de novo protein structure determinations for the successful generation of the correct polypeptide fold by the first CANDID cycle. Network-anchoring makes use of the fact that any network of correct NOE cross-peak assignments forms a self-consistent set; the initial, chemical shift-based assignments for each individual NOE cross-peak are therefore weighted by the extent to which they can be embedded into the network formed by all other NOE crosspeak assignments. Constraint-combination reduces the deleterious impact of artifact NOE upper distance constraints in the input for a protein structure calculation by combining the assignments for two or several peaks into a single upper limit distance constraint, which lowers the probability that the presence of an artifact peak will influence the outcome of the structure calculation. CANDID test calculations were performed with NMR data sets of four proteins for which high-quality structures had previously been solved by interactive protocols, and they yielded comparable results to these reference structure determinations with regard to both the residual constraint violations, and the precision and accuracy of the atomic coordinates. The CANDID approach has further been,validated by tie novo NMR structure determinations of four additional proteins. The experience gained in these calculations shows that once nearly complete sequence-specific resonance assignments are available, the automated CANDID approach results in greatly enhanced efficiency of the NOESY spectral analysis. The fact that the correct fold is obtained in cycle I of a tic novo structure calculation is the single most important advance achieved with CANDID, when compared with previously proposed automated NOESY assignment methods that do not use network-anchoring and constraint-combination. (C) 2002 Elsevier Science Ltd. All rights reserved.