Peptide–Membrane Binding: Effects of the Amino Acid Sequence
Peptide–Membrane Binding: Effects of the Amino Acid Sequence
复制标题
肽-膜结合：氨基酸序列的影响
DOI：
10.1021/acs.jpcb.2c06404
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Dias, Cristiano L.
中科院分区：
文献类型：
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作者：
Yang, Yanxing;Dias, Cristiano L.
氨基酸序列如何影响肽与脂质膜的相互作用的理解仍然是未知的。这种类型的知识是需要合理化膜诱导的淀粉样肽的毒性和设计肽，可以与脂质双层。在这里，我们进行了系统的研究如何在两亲性Ac-（FKFE）2-NH 2肽序列的变化影响其与两性离子脂质双层的相互作用，使用广泛的全原子分子动力学模拟在明确的溶剂。我们的研究结果表明，肽与净正电荷结合更频繁的脂质双层比中性或带负电荷的序列。此外，在序列的不同位置上用相同数量的苯丙氨酸（F）、赖氨酸（K）和谷氨酸（E）氨基酸制成的中性两亲肽在它们与膜结合的频率上显著不同。我们发现，如果肽的正赖氨酸侧链更多地暴露于溶剂，则肽以更高的频率与膜结合，如果它们位于序列的末端（而不是中间），则会发生这种情况。非极性残基在解释肽在膜上的吸附中起重要作用。特别地，用疏水性较低的非极性残基（例如，缬氨酸和丙氨酸）与用苯丙氨酸制备的肽相比，明显较少地吸附到膜上。我们还发现，苯丙氨酸残基位于肽的末端的序列具有更高的被吸附的倾向。
An understanding of how the amino acid sequence affects the interaction of peptides with lipid membranes remains mostly unknown. This type of knowledge is required to rationalize membrane-induced toxicity of amyloid peptides and to design peptides that can interact with lipid bilayers. Here, we perform a systematic study of how variations in the sequence of the amphipathic Ac-(FKFE)2-NH2peptide affect its interaction with zwitterionic lipid bilayers using extensive all-atom molecular dynamics simulations in explicit solvent. Our results show that peptides with a net positive charge bind more frequently to the lipid bilayer than neutral or negatively charged sequences. Moreover, neutral amphipathic peptides made with the same numbers of phenylalanine (F), lysine (K), and glutamic (E) amino acids at different positions in the sequence differ significantly in their frequency of binding to the membrane. We find that peptides bind with a higher frequency to the membrane if their positive lysine side chains are more exposed to the solvent, which occurs if they are located at the extremity (as opposed to the middle) of the sequence. Non-polar residues play an important role in accounting for the adsorption of peptides onto the membrane. In particular, peptides made with less hydrophobic non-polar residues (e.g., valine and alanine) are significantly less adsorbed to the membrane compared to peptides made with phenylalanine. We also find that sequences where phenylalanine residues are located at the extremities of the peptide have a higher tendency to be adsorbed.