Peptides designed with residues that have a high propensity to occur in β-turns form β-hairpin structures in apolar as well as in polar organic solvents such as dimethyl sulfoxide (DMSO). Due to limited solubility, their conformations have not been investigated experimentally in water. We have examined the conformations of four of such designed peptides that fold into well-defined β-hairpin structures facilitated by β-turns, in the crystalline state and in solution, by molecular dynamics simulations (MDS). The peptides folded into β-hairpin structures in water, starting from the fully extended conformation. However, in DMSO, neither folding nor unfolding was observed during MDS, when the starting structures were unfolded and folded, respectively. The lack of folding in DMSO was investigated by constructing folding free energy landscapes by umbrella sampling. The folding free energy landscape is smooth in water, whereas in DMSO, folded and unfolded structures are separated by high-energy barriers. The folding free energy is less in DMSO compared with water due to a more stable unfolded structure in DMSO compared with water, which in turn is due to stabilisation of the unfolded state by hydrophobic interactions in DMSO. This finding will be helpful to researchers to accurately model and/or design small peptide structures in water and organic solvents.

中文翻译：

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在溶液中形成β-发夹结构的疏水肽的计算机折叠

设计有在 β 转角中容易出现的残基的肽在非极性和极性有机溶剂如二甲亚砜 (DMSO) 中形成 β 发夹结构。由于溶解度有限，它们的构象尚未在水中进行实验研究。我们已经通过分子动力学模拟（MDS）检查了四种此类设计的肽的构象，这些肽在结晶状态和溶液中折叠成由β-转角促进的明确定义的β-发夹结构。肽在水中折叠成β-发夹结构，从完全延伸的构象开始。然而，在 DMSO 中，当起始结构分别展开和折叠时，在 MDS 期间既未观察到折叠也未观察到展开。通过伞形采样构建折叠自由能景观，研究了 DMSO 中缺乏折叠的情况。折叠自由能景观在水中是平滑的，而在 DMSO 中，折叠和展开结构被高能屏障隔开。与水相比，DMSO 中的折叠自由能较低，这是因为 DMSO 中的未折叠结构比水更稳定，这反过来是由于 DMSO 中的疏水相互作用使未折叠状态稳定。这一发现将有助于研究人员准确地模拟和/或设计水和有机溶剂中的小肽结构。与水相比，DMSO 中的折叠自由能较低，这是因为 DMSO 中的未折叠结构比水更稳定，这反过来是由于 DMSO 中的疏水相互作用使未折叠状态稳定。这一发现将有助于研究人员准确地模拟和/或设计水和有机溶剂中的小肽结构。与水相比，DMSO 中的折叠自由能较低，这是因为 DMSO 中的未折叠结构比水更稳定，这反过来是由于 DMSO 中的疏水相互作用使未折叠状态稳定。这一发现将有助于研究人员准确地模拟和/或设计水和有机溶剂中的小肽结构。