van der Spoel D, Berendsen H J
Bioson Research Institute, University of Groningen, The Netherlands.
Biophys J. 1997 May;72(5):2032-41. doi: 10.1016/S0006-3495(97)78847-7.
The structure of Leu-enkephalin (L-Enk) and Met-enkephalin (M-Enk) have frequently been studied, in particular by nuclear magnetic resonance spectroscopy. After more than 20 years of research, it was concluded that enkephalins have no preferred structure in aqueous solution, but that they may have in other solvents. We have performed molecular dynamics simulations of zwitterionic L-Enk in water, and zwitterionic as well as neutral L-Enk dimethyl sulfoxide (DMSO). In water the peptide is very flexible, although there seems to be a preference for compact conformations. In DMSO, the peptide forms a clear salt bridge in the zwitterionic form, but has no preferred conformation in the neutral form. This difference in conformation may provide an explanation for measurements in DMSO in which multiple conformations were found to exist. In this paper we introduce a new formulation for a dihedral angle autocorrelation function, and apply it to study side-chain dynamics in L-Enk. We find that the side-chain dynamics of the large Tyr and Phe residues cannot be adequately sampled in 2.0-ns simulations, while this does seem to be possible for the smaller Leu side chain.
亮氨酸脑啡肽（L-Enk）和甲硫氨酸脑啡肽（M-Enk）的结构经常被研究，尤其是通过核磁共振光谱法。经过20多年的研究，得出的结论是，脑啡肽在水溶液中没有偏好的结构，但在其他溶剂中可能有。我们对水中的两性离子L-Enk以及两性离子和中性L-Enk在二甲基亚砜（DMSO）中进行了分子动力学模拟。在水中，肽非常灵活，尽管似乎偏好紧凑的构象。在DMSO中，肽以两性离子形式形成明显的盐桥，但在中性形式下没有偏好的构象。这种构象差异可能为在DMSO中发现存在多种构象的测量结果提供解释。在本文中，我们引入了一种新的二面角自相关函数公式，并将其应用于研究L-Enk中的侧链动力学。我们发现，在2.0纳秒的模拟中，大的酪氨酸（Tyr）和苯丙氨酸（Phe）残基的侧链动力学无法得到充分采样，而较小的亮氨酸（Leu）侧链似乎是可以的。
