Nandel Fateh S, Garg Mohan L, Shafique Mohd
Department of Biophysics, Panjab University, Chandigarh, 160014, India,
J Mol Model. 2015 May;21(5):123. doi: 10.1007/s00894-015-2671-8. Epub 2015 Apr 23.
Oculopharyngeal muscular dystrophy (OPMD), a polyalanine myopathy, occurs due to expansion of homo-polyalanine stretch in normal polyadenylating binding protein nuclear 1 (PABPN1) protein from Ala10 to Ala11-17. Therefore, the conformational behavior of polyalanine peptides with n = 10-17, with and without terminal protecting groups, have been investigated with different starting geometries in water by molecular dynamics simulation studies. Alanine peptides are shown to give rise to unordered structure irrespective of starting geometry and not more than two residues at a stretch have the same/similar set of φ, ψ values. However, the final structure with terminal protecting groups look like β-strand. Unprotected poly-Ala peptides adopt twisted β-hairpin/multi hairpin like structure with increasing chain length. The number of residues having φ, ψ values in collagen region is found to be less in peptides with unprotected termini as compared to peptides with protected termini of same chain length. The results have been supported by recent synchrotron radiation circular dichroism spectroscopy of polyproline II and unordered secondary structures. Opening of the helical structure in poly-Ala peptides with protecting groups has been shown to take place from C-terminal and in peptides without protecting groups opening of helix starts from both terminals. Further, opening of helix takes more time in poly-Ala peptides without terminal protecting groups. The deviations in amide bond planarity have been discussed and compared with available experimental and computational results.
眼咽型肌营养不良症（OPMD）是一种多聚丙氨酸肌病，它是由于正常的聚腺苷酸结合蛋白核1（PABPN1）蛋白中的同聚丙氨酸片段从丙氨酸10扩展到丙氨酸11 - 17而引发的。因此，通过分子动力学模拟研究，我们在水中以不同的起始几何结构，对n = 10 - 17、带有和不带有末端保护基的多聚丙氨酸肽的构象行为进行了研究。结果表明，无论起始几何结构如何，丙氨酸肽都会形成无序结构，且连续的残基中不超过两个具有相同/相似的φ、ψ值。然而，带有末端保护基的最终结构看起来像β链。未保护的聚丙氨酸肽随着链长增加会采用扭曲的β发夹/多发夹样结构。与相同链长但带有保护末端的肽相比，发现未保护末端的肽在胶原蛋白区域具有φ、ψ值的残基数量更少。这些结果得到了最近关于多聚脯氨酸II和无序二级结构的同步辐射圆二色光谱的支持。带有保护基的聚丙氨酸肽的螺旋结构从C端开始打开，而没有保护基的肽的螺旋从两端开始打开。此外，没有末端保护基的聚丙氨酸肽的螺旋打开需要更多时间。我们还讨论了酰胺键平面性的偏差，并与现有的实验和计算结果进行了比较。
