Daura X, Gademann K, Schäfer H, Jaun B, Seebach D, van Gunsteren W F
Contribution from the Laboratory of Physical Chemistry, Swiss Federal Institute of Technology Zurich, ETH-Zentrum, CH-8092 Zurich, Switzerland.
J Am Chem Soc. 2001 Mar 14;123(10):2393-404. doi: 10.1021/ja003689g.
The structural and thermodynamic properties of a 6-residue beta-peptide that was designed to form a hairpin conformation have been studied by NMR spectroscopy and MD simulation in methanol solution. The predicted hairpin would be characterized by a 10-membered hydrogen-bonded turn involving residues 3 and 4, and two extended antiparallel strands. The interproton distances and backbone torsional dihedral angles derived from the NMR experiments at room temperature are in general terms compatible with the hairpin conformation. Two trajectories of system configurations from 100-ns molecular-dynamics simulations of the peptide in solution at 298 and 340 K have been analyzed. In both simulations reversible folding to the hairpin conformation is observed. Interestingly, there is a significant conformational overlap between the unfolded state of the peptide at each of the temperatures. As already observed in previous studies of peptide folding, the unfolded state is composed of a (relatively) small number of predominant conformers and in this case lacks any type of secondary-structure element. The trajectories provide an excellent ground for the interpretation of the NMR-derived data in terms of ensemble averages and distributions as opposed to single-conformation interpretations. From this perspective, a relative population of the hairpin conformation of 20% to 30% would suffice to explain the NMR-derived data. Surprisingly, however, the ensemble of structures from the simulation at 340 K reproduces more accurately the NMR-derived data than the ensemble from the simulation at 298 K, a question that needs further investigation.
通过核磁共振光谱法和甲醇溶液中的分子动力学模拟，研究了一种设计用于形成发夹构象的6残基β-肽的结构和热力学性质。预测的发夹结构的特征是由涉及残基3和4的10元氢键转角以及两条延伸的反平行链组成。室温下核磁共振实验得出的质子间距离和主链扭转二面角总体上与发夹构象相符。分析了该肽在298 K和340 K溶液中100 ns分子动力学模拟的两条系统构型轨迹。在这两种模拟中均观察到向发夹构象的可逆折叠。有趣的是，在每个温度下肽的未折叠状态之间存在明显的构象重叠。正如先前在肽折叠研究中所观察到的，未折叠状态由（相对）少数主要构象组成，并且在这种情况下缺乏任何类型的二级结构元件。这些轨迹为根据系综平均值和分布而不是单一构象解释来解释核磁共振数据提供了极好的基础。从这个角度来看，发夹构象20%至30%的相对丰度足以解释核磁共振数据。然而，令人惊讶的是，340 K模拟得到的结构系综比298 K模拟得到的系综更准确地再现了核磁共振数据，这一问题需要进一步研究。
