Binary patterning of polar and nonpolar amino acids in the sequences and structures of native proteins.
Binary patterning of polar and nonpolar amino acids in the sequences and structures of native proteins.
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天然蛋白质序列和结构中极性和非极性氨基酸的二元模式。
DOI：
10.1002/pro.5560041008
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Hecht,MH
中科院分区：
文献类型：
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作者：
West,MW;Hecht,MH
蛋白质序列可以表示为极性（〇）和非极性（•）氨基酸的二元模式。这些二元序列模式分为两类：A类模式匹配理想两亲性α‐螺旋的结构重复（每转3.6个残基），B类模式匹配理想两亲性β‐链的结构重复（每转2个残基）。这两类序列模式之间的差异导致了一种基于极性和非极性氨基酸二元模式的从头蛋白质设计策略。在这里，我们问是否类似的二进制模式是合并在序列和结构的天然蛋白质。对蛋白质数据库的分析表明：(1) A类序列模式在天然蛋白质序列中出现的频率比随机预测的要高得多，而B类序列模式出现的频率比随机预测的要低。(2)每种模式主要存在于蛋白质设计的二元策略所期望的二级结构中。因此，A类模式在α‐螺旋中比在β‐螺旋中更常见，B类模式在β‐螺旋中比在α‐螺旋中更常见。(3)在天然蛋白质的α‐螺旋结构中，最常用的二元模式确实是A类模式。(4)在数据库中的所有β‐链中，最常用的二元模式并不是预期的B类模式。(5)然而，对于溶剂暴露的β链，相关性是惊人的：数据库中包含B类模式的所有β链都暴露于溶剂。(6) α‐结构的A类模式相对于β‐结构的偏倚和β‐结构的B类模式相对于α‐结构的偏倚是显著的，不仅仅是与其他极性（〇）和非极性（•）氨基酸的二元模式相比，而且与数据库中的全部序列相比也是如此。讨论了对新型蛋白质设计的启示。
Protein sequences can be represented as binary patterns of polar (○) and nonpolar (•) amino acids. These binary sequence patterns are categorized into two classes: Class A patterns match the structural repeat of an idealized amphiphilic α‐helix (3.6 residues per turn), and class B patterns match the structural repeat of an idealized amphiphilic β‐strand (2 residues per turn). The difference between these two classes of sequence patterns has led to a strategy for de novo protein design based on binary patterning of polar and nonpolar amino acids. Here we ask whether similar binary patterning is incorporated in the sequences and structures of natural proteins. Analysis of the Protein Data Bank demonstrates the following. (1) Class A sequence patterns occur considerably more frequently in the sequences of natural proteins than would be expected at random, but class B patterns occur less often than expected. (2) Each pattern is found predominantly in the secondary structure expected from the binary strategy for protein design. Thus, class A patterns are found more frequently in α‐helices than in β‐strands, and class B patterns are found more frequently in β‐strands than in α‐helices. (3) Among the α‐helices of natural proteins, the most commonly used binary patterns are indeed the class A patterns. (4) Among all β‐strands in the database, the most commonly used binary patterns are not the expected class B patterns. (5) However, for solvent‐exposed β‐strands, the correlation is striking: All β‐strands in the database that contain the class B patterns are exposed to solvent. (6) The bias of class A patterns for α‐structure over β‐structure and the bias of class B patterns for β‐structure over α‐structure are significant, not merely when compared to other binary patterns of polar (○) and nonpolar (•) amino acids, but also when compared to the full range of sequences in the database. The implications for the design of novel proteins are discussed.