A linguistic model for the rational design of antimicrobial peptides
A linguistic model for the rational design of antimicrobial peptides
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DOI：
10.1038/nature05233
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发表时间：
2006-10-19
期刊：
影响因子：
64.8
通讯作者：
Stephanopoulos, Gregory
中科院分区：
文献类型：
--
作者：
Loose, Christopher;Jensen, Kyle;Stephanopoulos, Gregory
抗微生物肽（AmPs）是先天免疫系统用于对抗多细胞真核生物中细菌感染的小蛋白质（1）。越来越多的证据表明，这些肽比传统抗生素对细菌耐药性更不敏感，可以形成一类新的治疗药物的基础（2）。在这里，我们报告了新的安培的合理设计，显示有限的同源性，天然存在的蛋白质，但有很强的抑菌活性对几种细菌，包括金黄色葡萄球菌和炭疽杆菌。这些肽是使用天然AmPs的语言模型设计的：我们将天然AmPs的氨基酸序列视为一种形式语言，并建立了一组规则语法来描述这种语言。我们使用这组语法来创建新的、非自然的AmP序列。我们的肽符合天然抗菌肽的正式语法，但填充了蛋白质序列空间的一个以前未探索的区域。
Antimicrobial peptides (AmPs) are small proteins that are used by the innate immune system to combat bacterial infection in multicellular eukaryotes(1). There is mounting evidence that these peptides are less susceptible to bacterial resistance than traditional antibiotics and could form the basis for a new class of therapeutic agents(2). Here we report the rational design of new AmPs that show limited homology to naturally occurring proteins but have strong bacteriostatic activity against several species of bacteria, including Staphylococcus aureus and Bacillus anthracis. These peptides were designed using a linguistic model of natural AmPs: we treated the amino-acid sequences of natural AmPs as a formal language and built a set of regular grammars to describe this language. We used this set of grammars to create new, unnatural AmP sequences. Our peptides conform to the formal syntax of natural antimicrobial peptides but populate a previously unexplored region of protein sequence space.