Exploring the sequence space for (tri-) peptide self-assembly to design and discover
Exploring the sequence space for (tri-) peptide self-assembly to design and discover
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DOI：
10.1038/nchem.2122
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发表时间：
2015-01-01
期刊：
影响因子：
21.8
通讯作者：
Tuttle, Tell
中科院分区：
文献类型：
--
作者：
Frederix, Pim W. J. M.;Scott, Gary G.;Tuttle, Tell
自组装成纳米结构的肽在生物学、医学、光子学和纳米技术应用中具有巨大的兴趣。从20个氨基酸中获得的巨大序列空间可能包含许多有趣的候选者，但目前不可能仅从序列预测超分子行为。在这里，我们展示了计算工具来筛选所有8，000种可能的三肽中的水自组装倾向，并通过与已知实例的比较来评估这些。我们应用过滤器来选择候选人，同时优化聚集倾向和亲水性的明显矛盾的要求，这导致了一组自组装序列的设计规则。随后合成和表征了许多肽，包括第一次报道的能够在中性pH下形成水凝胶的三肽。这些工具使肽序列空间能够搜索超分子性质，使极简的肽纳米技术能够实现其承诺。
Peptides that self-assemble into nanostructures are of tremendous interest for biological, medical, photonic and nanotechnological applications. The enormous sequence space that is available from 20 amino acids probably harbours many interesting candidates, but it is currently not possible to predict supramolecular behaviour from sequence alone. Here, we demonstrate computational tools to screen for the aqueous self-assembly propensity in all of the 8,000 possible tripeptides and evaluate these by comparison with known examples. We applied filters to select for candidates that simultaneously optimize the apparently contradicting requirements of aggregation propensity and hydrophilicity, which resulted in a set of design rules for self-assembling sequences. A number of peptides were subsequently synthesized and characterized, including the first reported tripeptides that are able to form a hydrogel at neutral pH. These tools, which enable the peptide sequence space to be searched for supramolecular properties, enable minimalistic peptide nanotechnology to deliver on its promise.