Prediction in 1D: secondary structure, membrane helices, and accessibility.
Prediction in 1D: secondary structure, membrane helices, and accessibility.
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DOI：
10.1002/0471721204.ch28
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发表时间：
2003
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影响因子：
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通讯作者：
B. Rost
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文献类型：
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作者：
B. Rost
还没有从序列中预测三维（3D）结构的通用方法。蛋白质的3D结构（折叠）由序列的特异性唯一决定的假设已经在许多蛋白质中得到验证（Anfinsen，1973）。虽然现在已知特定的蛋白质（分子伴侣）通常在折叠中起重要作用（科拉莱斯和Fersht，1996; Martin和Hartl，1997; Ellis，多布森和Hartl，1998），但通常仍然认为最终结构处于自由能最小值（多布森和Karplus，1999）。因此，关于蛋白质天然结构的所有信息都编码在氨基酸序列中，加上其天然溶液环境。我们能破译密码吗？因此，我们可以从序列预测3D结构吗？原则上，该代码可以从物理化学原理中破译（Levitt和Warshel，1975; Hagler和Honig，1978）。在实践中，实验确定基本参数的不准确性和有限的计算资源阻止了从第一原理预测蛋白质结构（货车Gunsteren，1993）。因此，唯一成功的结构预测工具是基于知识的，使用统计理论和经验规则的组合。蛋白质结构预测领域在20世纪90年代取得了重大进展（见第27章）。然而，我们仍然不能从序列预测结构。相反，现在最好的方法是在某些时候正确地获得褶皱的基本特征（CASP 4，2000; Lesk，Lo Conte，and Hubbard，2001）。
No general prediction of three-dimensional (3D) structure from sequence yet. The hypothesis that the 3D structure1 of a protein (the fold) is uniquely determined by the specificity of the sequence has been verified for many proteins (Anfinsen, 1973). While it is now known that particular proteins (chaperones) often play an important role in folding (Corrales and Fersht, 1996; Martin and Hartl, 1997; Ellis, Dobson, and Hartl, 1998), it is still generally assumed that the final structure is at the freeenergy minimum (Dobson and Karplus, 1999). Thus, all information about the native structure of a protein is coded in the amino acid sequence, plus its native solution environment. Can we decipher the code? Hence, can we predict 3D structure from sequence? In principle, the code could by deciphered from physicochemical principles (Levitt and Warshel, 1975; Hagler and Honig, 1978). In practice, the inaccuracy in experimentally determining the basic parameters and the limited computing resources prevent prediction of protein structure from first principles (van Gunsteren, 1993). Therefore, the only successful structure prediction tools are knowledge-based, using a combination of statistical theory and empirical rules. The field of protein structure prediction advanced significantly during the 1990s (see Chapter 27). However, we can still not predict structure from sequence. Rather, the best methods now get the basic characteristics about a fold right some of the time (CASP4, 2000; Lesk, Lo Conte, and Hubbard, 2001).