Ph.D. Program in Biochemistry, The Graduate Center of the City University of New York, New York, New York 10016, United States.
Department of Materials Science and Engineering, University of Central Florida, 4000 Central Florida Boulevard, Orlando, FL 32816, United States.
Biomacromolecules. 2024 Mar 11;25(3):1468-1480. doi: 10.1021/acs.biomac.3c01032. Epub 2024 Feb 17.
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 Tabandeh 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.
聚电解质复合物（PECs）由于其在开发新型自适应材料中的应用及其在无膜细胞器中的相关性而备受关注。这些复合物在带相反电荷的聚合物在水介质中混合时出现相分离。基于肽的 PEC 由于其固有生物相容性，对于开发新的药物输送方法特别有用。可以调整基础肽序列以优化复合物的特定材料特性，例如界面张力和粘度。鉴于其适用性，了解带相反电荷的肽的序列依赖性相行为将是有利的。在这里，我们报告了微秒分子动力学模拟，以表征疏水性对模型多肽序列的序列依赖性肽构象的影响，这些序列是由 Tabandeh 先前报道的。这些序列的设计具有肽主链交替的手性。我们对六个带相反电荷的肽对进行了微秒模拟，表征了对肽大小、氢键程度、二级结构和构象的序列依赖性影响。这种分析再现了肽构象和氢键程度的合理趋势，与实验报告的结果一致。Ramachandran 图揭示了在单氨基酸水平上的骨架构象受链中相邻序列的高度影响。这些结果深入了解了疏水性侧链大小和手性的微小变化如何影响链之间氢键的强度，最终影响二级结构。此外，主成分分析表明，潜在序列可能微妙地调节最小能量结构。
