Improved Descriptors for the Quantitative Structure-Activity Relationship Modeling of Peptides and Proteins
Improved Descriptors for the Quantitative Structure-Activity Relationship Modeling of Peptides and Proteins
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DOI：
10.1021/acs.jcim.7b00488
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发表时间：
2018-02-01
影响因子：
5.6
通讯作者：
Goodacre, Royston
中科院分区：
文献类型：
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作者：
Barley, Mark H.;Turner, Nicholas J.;Goodacre, Royston
使用定量结构活性关系(QSAR)对蛋白质的活性进行建模的能力需要20个自然编码的氨基酸的描述符。在这项工作中，我们表明，通过修改一些已建立的描述符，我们能够以更高的准确性对140个酶环氧化物水解酶突变体的活性数据进行建模。这些新的描述符(称为物理描述符)在与一系列四个二肽数据集进行测试时也给出了非常好的结果。物理描述符仅使用两个正交表对氨基酸进行编码：第一个与亲水性/疏水性密切相关，第二个与氨基酸残基的体积密切相关。这些新的氨基酸描述符的使用应该会导致对多肽和蛋白质的酶活性(以及潜在的其他感兴趣的功能，例如二级和三级结构)的更简单和更容易解释的模型。
The ability to model the activity of a protein using quantitative structure activity relationships (QSAR) requires descriptors for the 20 naturally coded amino acids. In this work we show that by modifying some established descriptors we were able to model the activity data of 140 mutants of the enzyme epoxide hydrolase with improved accuracy. These new descriptors (referred to as physical descriptors) also gave very good results when tested against a series of four dipeptide data sets. The physical descriptors encode the amino acids using only two orthogonal scales: the first is strongly linked to hydrophilicity/hydrophobicity, and the second, to the volume of the amino acid residue. The use of these new amino acid descriptors should result in simpler and more readily interpretable models for the enzyme activity (and potentially other functions of interest, e.g., secondary and tertiary structure) of peptides and proteins.