Moral Rimjhim, Paul Sandip
Department of Chemistry, Indian Institute of Technology, Guwahati, Assam 781039, India.
J Phys Chem B. 2025 Apr 10;129(14):3590-3603. doi: 10.1021/acs.jpcb.5c00400. Epub 2025 Mar 27.
Cyclic peptides (CPs) possess the ability to self-assemble into cyclic peptide nanotubes (CPNTs), which find extensive applications in nanotechnology. The formation and stability of these nanotubes are influenced by multiple factors. The present study explores the stability of CPNTs in various solvents with varying polarity, focusing on three specific peptide sequences: D, W, and DK. Using molecular dynamics simulations, the effect of solvent polarity and peptide composition on the stability of CPNTs is assessed through the determination of electrostatic, van der Waals, and hydrogen-bonding interactions. The binding free energy between adjacent cyclic peptide rings is analyzed via MM/GBSA and MM/PBSA methods, revealing that DK, an amphiphilic peptide, exhibits greater stability than D and W in nonpolar solvents. The introduction of leucine residues in DK reduces intramolecular hydrogen bonding and electrostatic interactions, promoting stronger interpeptide backbone hydrogen bonds and maintaining the nanotube's structural integrity. Hydrogen bond lifetimes, computed using the corresponding time correlation function, indicate the longest-lasting hydrogen bonds occur in all the solvent environments except water, further contributing to the stability of DK nanotubes. Additionally, deformation from circularity in the peptide rings, analyzed using ellipticity values, highlights the degree of structural distortion across solvents, with D showing the highest deviation due to stronger intramolecular interactions. These findings offer valuable insights into the roles of solvent and peptide composition in the self-assembly and stability of CPNTs, which have significant implications for their potential applications in nanotechnology and biomedicine.
环肽（CPs）具有自组装成环肽纳米管（CPNTs）的能力，而环肽纳米管在纳米技术中有着广泛的应用。这些纳米管的形成和稳定性受到多种因素的影响。本研究探讨了CPNTs在不同极性溶剂中的稳定性，重点关注三个特定的肽序列：D、W和DK。通过分子动力学模拟，通过测定静电、范德华和氢键相互作用，评估了溶剂极性和肽组成对CPNTs稳定性的影响。通过MM/GBSA和MM/PBSA方法分析了相邻环肽环之间的结合自由能，结果表明，两亲性肽DK在非极性溶剂中比D和W表现出更高的稳定性。在DK中引入亮氨酸残基减少了分子内氢键和静电相互作用，促进了更强的肽间主链氢键形成，并维持了纳米管的结构完整性。使用相应的时间相关函数计算的氢键寿命表明，除水以外的所有溶剂环境中都存在持续时间最长的氢键，这进一步有助于DK纳米管的稳定性。此外，使用椭圆率值分析肽环的圆度变形，突出了不同溶剂中结构扭曲的程度，由于分子内相互作用较强，D表现出最高的偏差。这些发现为溶剂和肽组成在CPNTs自组装和稳定性中的作用提供了有价值的见解，这对它们在纳米技术和生物医学中的潜在应用具有重要意义。
