Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Sendai, Miyagi 981-8558, Japan.
J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Nov 1;879(29):3337-43. doi: 10.1016/j.jchromb.2011.08.011. Epub 2011 Aug 17.
Molecular dynamics simulations of amyloid β(1-42) containing D-aspartic acid residues were performed using several continuous solvent models to investigate the usefulness of simulation methods for D-amino acid-containing proteins and peptides. Normal molecular dynamics simulations and replica exchange molecular dynamics simulations, which are one of the generalized-ensemble algorithms, were performed. Because the β-structure contents of amyloid β(1-42) peptides obtained by replica exchange molecular dynamics simulations with Onufriev-Bashford-Case generalized Born implicit solvent were qualitatively consistent with experimental data, replica exchange molecular dynamics rather than other methods appeared to be more reasonable for calculations of amyloid β(1-42) containing D-aspartic acid residues. Computational results revealed that peptides with stereoinversion of Asp23 tend to form β-sheet structures by themselves, in contrast to the wild-type peptides that form β-sheet structures only after aggregation. These results are expected to be useful for computational investigations of proteins and peptides such as prediction of retention time of peptides and proteins containing D-aspartic acid residues.
采用几种连续溶剂模型对含有 D-天冬氨酸残基的淀粉样 β(1-42)进行了分子动力学模拟，以研究模拟方法在含有 D-氨基酸的蛋白质和肽中的有用性。进行了常规分子动力学模拟和复制交换分子动力学模拟，复制交换分子动力学模拟是广义系综算法之一。由于使用 Onufriev-Bashford-Case 广义 Born 隐溶剂的复制交换分子动力学模拟获得的淀粉样 β(1-42)肽的β-结构含量与实验数据定性一致，因此复制交换分子动力学模拟而不是其他方法似乎更适合于计算含有 D-天冬氨酸残基的淀粉样 β(1-42)。计算结果表明，立体反转的 Asp23 肽倾向于自身形成 β-折叠结构，而野生型肽只有在聚集后才形成 β-折叠结构。这些结果有望用于对蛋白质和肽的计算研究，例如预测含有 D-天冬氨酸残基的肽和蛋白质的保留时间。
