Cornilescu G, Delaglio F, Bax A
Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520, USA.
J Biomol NMR. 1999 Mar;13(3):289-302. doi: 10.1023/a:1008392405740.
Chemical shifts of backbone atoms in proteins are exquisitely sensitive to local conformation, and homologous proteins show quite similar patterns of secondary chemical shifts. The inverse of this relation is used to search a database for triplets of adjacent residues with secondary chemical shifts and sequence similarity which provide the best match to the query triplet of interest. The database contains 13C alpha, 13C beta, 13C', 1H alpha and 15N chemical shifts for 20 proteins for which a high resolution X-ray structure is available. The computer program TALOS was developed to search this database for strings of residues with chemical shift and residue type homology. The relative importance of the weighting factors attached to the secondary chemical shifts of the five types of resonances relative to that of sequence similarity was optimized empirically. TALOS yields the 10 triplets which have the closest similarity in secondary chemical shift and amino acid sequence to those of the query sequence. If the central residues in these 10 triplets exhibit similar phi and psi backbone angles, their averages can reliably be used as angular restraints for the protein whose structure is being studied. Tests carried out for proteins of known structure indicate that the root-mean-square difference (rmsd) between the output of TALOS and the X-ray derived backbone angles is about 15 degrees. Approximately 3% of the predictions made by TALOS are found to be in error.
蛋白质中主链原子的化学位移对局部构象极为敏感，同源蛋白质呈现出颇为相似的二级化学位移模式。利用这种关系的逆过程，在数据库中搜索具有二级化学位移和序列相似性的相邻残基三联体，以找到与感兴趣的查询三联体最匹配的结果。该数据库包含20种蛋白质的13Cα、13Cβ、13C'、1Hα和15N化学位移，这些蛋白质都有高分辨率的X射线结构。开发了计算机程序TALOS，用于在该数据库中搜索具有化学位移和残基类型同源性的残基串。相对于序列相似性，对五种类型共振的二级化学位移所附加的加权因子的相对重要性进行了经验优化。TALOS会给出与查询序列在二级化学位移和氨基酸序列上最相似的10个三联体。如果这10个三联体中的中心残基表现出相似的φ和ψ主链角，那么它们的平均值可以可靠地用作正在研究其结构的蛋白质的角度约束。对已知结构的蛋白质进行的测试表明，TALOS的输出结果与X射线衍生的主链角之间的均方根偏差（rmsd）约为15度。发现TALOS所做的预测中约有3%是错误的。
