Molecular Dynamics Simulations of Polyelectrolyte Complexes
Molecular Dynamics Simulations of Polyelectrolyte Complexes
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DOI：
10.1021/acs.biomac.3c01032
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发表时间：
2024-02-17
影响因子：
6.2
通讯作者：
Loverde，Sharon M.
中科院分区：
文献类型：
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作者：
Rajpersaud，Tania;Tabandeh，Sara;Loverde，Sharon M.
聚电解质复合体(PECs)因其在开发新的适应性材料方面的应用以及在无膜细胞器中的应用而引起人们的极大兴趣。当相反电荷的聚合物混合在水介质中时，在相分离过程中会出现这些络合物。基于多肽的PECs由于其固有的生物相容性，在开发新的药物传递方法方面特别有用。潜在的多肽序列可以进行调整，以优化复合体的特定材料属性，如界面张力和粘度。考虑到它们的适用性，了解反电荷肽潜在的序列依赖相行为将是有利的。在这里，我们报告了微秒分子动力学模拟来表征疏水性对Tabandehet等人先前报道的模型多肽序列依赖于序列的多肽构象的影响。这些序列被设计为具有交替手性的多肽骨架。我们提供了六个带相反电荷的多肽对的微秒模拟，表征了序列对多肽大小、氢键程度、二级结构和构象的影响。这一分析概括了多肽构象和氢键程度的合理趋势，与实验报告的结果一致。Ramachandran图表明，单一氨基酸水平上的骨架构象受链上相邻序列的影响很大。这些结果揭示了疏水侧链大小和手性的细微变化如何影响链之间的氢键强度，并最终影响二级结构。此外，主成分分析表明，最小能量结构可能受到潜在序列的微妙调制。
Polyelectrolyte complexes (PECs) are currently of great interest due to their applications toward developing new adaptive materials and their relevance in membraneless organelles. These complexes emerge during phase separation when oppositely charged polymers are mixed in aqueous media. Peptide-based PECs are particularly useful toward developing new drug delivery methods due to their inherent biocompatibility. The underlying peptide sequence can be tuned to optimize specific material properties of the complex, such as interfacial tension and viscosity. Given their applicability, it would be advantageous to understand the underlying sequence-dependent phase behavior of oppositely charged peptides. Here, we report microsecond molecular dynamic simulations to characterize the effect of hydrophobicity on the sequence-dependent peptide conformation for model polypeptide sequences that were previously reported by Tabandehet al.These sequences are designed with alternating chirality of the peptide backbone. We present microsecond simulations of six oppositely charged peptide pairs, characterizing the sequence-dependent effect on peptide size, degree of hydrogen bonding, secondary structure, and conformation. This analysis recapitulates sensible trends in peptide conformation and degree of hydrogen bonding, consistent with experimentally reported results. Ramachandran plots reveal that backbone conformation at the single amino acid level is highly influenced by the neighboring sequence in the chain. These results give insight into how subtle changes in hydrophobic side chain size and chirality influence the strength of hydrogen bonding between the chains and, ultimately, the secondary structure. Furthermore, principal component analysis reveals that the minimum energy structures may be subtly modulated by the underlying sequence.