Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India.
J Phys Chem B. 2020 Nov 12;124(45):10048-10061. doi: 10.1021/acs.jpcb.0c06000. Epub 2020 Oct 28.
Generally, hydrophobic amino acids provide hydrophobic interactions during peptide aggregation. However, besides the hydrophobic amino acids, some hydrophilic amino acids, such as glutamine, are also considered to be essential elements in many self-aggregating peptides. For example, huntingtin contains polyglutamine at its N-terminus and the yeast prion Sup35 protein has the GNNQQNY sequence, a peptide well-known for its ability for amyloid fibril formation. However, despite the frequent emergence of glutamine in self-assembling systems, the molecular mechanism of amyloid formation involving this unique amino acid has not been well documented. It is still not clear how this hydrophilic amino acid is responsible for the hydrophobic interaction in the self-association process. Therefore, in this study, we have carried out classical molecular dynamics simulations of the GNNQQNY peptide and its derivatives in pure water. We quantify the propensity for the formation of β-sheet conformation with an increasing glutamine number in the peptide sequence. In addition, we assess the importance of the hydrophobicity of the dimethanediyl group present in glutamine (as well as in glutamic acid) for the self-association of the peptides through nonpolar solvent medium simulations.
一般来说，疏水性氨基酸在肽聚集过程中提供疏水性相互作用。然而，除了疏水性氨基酸外，一些亲水性氨基酸，如谷氨酰胺，也被认为是许多自聚集肽的必需元素。例如，亨廷顿蛋白在其 N 端含有聚谷氨酰胺，酵母朊病毒 Sup35 蛋白具有 GNNQQNY 序列，该肽以其形成淀粉样纤维的能力而闻名。然而，尽管在自组装系统中经常出现谷氨酰胺，但涉及这种独特氨基酸的淀粉样形成的分子机制尚未得到很好的记录。目前尚不清楚这种亲水性氨基酸如何负责自缔合过程中的疏水性相互作用。因此，在这项研究中，我们在纯水中对 GNNQQNY 肽及其衍生物进行了经典的分子动力学模拟。我们通过增加肽序列中谷氨酰胺的数量来量化形成 β-折叠构象的趋势。此外，我们通过非极性溶剂介质模拟评估了存在于谷氨酰胺（以及谷氨酸）中的二甲亚基的疏水性对肽自组装的重要性。
