Effect of urea on peptide conformation in water: Molecular dynamics and experimental characterization
Effect of urea on peptide conformation in water: Molecular dynamics and experimental characterization
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DOI：
10.1529/biophysj.105.061978
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发表时间：
2005-08-01
影响因子：
3.4
通讯作者：
Nilsson, L
中科院分区：
文献类型：
--
作者：
Caballero-Herrera, A;Nordstrand, K;Nilsson, L
核糖核酸酶A的C-肽类似物和序列变体的分子动力学模拟进行了在水中在277和300 K和8 M尿素，以澄清尿素诱导的分子变性机制和蛋白质展开的早期事件。肽的光谱表征显示C-肽类似物具有高α-螺旋含量，而变体的情况并非如此。在模拟中，相互依赖的侧链相互作用是负责在不同溶剂中的α-螺旋C-肽类似物的高稳定性。另一种肽显示α-螺旋解旋，其向N-末端协同传播。由肽采样的构象取决于它们的序列和溶剂。在尿素存在下，水分子与肽形成氢键的能力以及氢键寿命增加，而肽附近的水流动性降低。尿素在肽周围过量积累，与肽形成长寿命的氢键。由热变性和尿素诱导的解折叠机制具有不同的性质，尿素水溶液提供比纯水更好的肽溶剂化。结果表明，尿素对化学变性过程的影响包括直接和间接两种机制。
Molecular dynamics simulations of a ribonuclease A C-peptide analog and a sequence variant were performed in water at 277 and 300 K and in 8 M urea to clarify the molecular denaturation mechanism induced by urea and the early events in protein unfolding. Spectroscopic characterization of the peptides showed that the C-peptide analog had a high alpha-helical content, which was not the case for the variant. In the simulations, interdependent side-chain interactions were responsible for the high stability of the alpha-helical C-peptide analog in the different solvents. The other peptide displayed alpha-helical unwinding that propagated cooperatively toward the N-terminal. The conformations sampled by the peptides depended on their sequence and on the solvent. The ability of water molecules to form hydrogen bonds to the peptide as well as the hydrogen bond lifetimes increased in the presence of urea, whereas water mobility was reduced near the peptide. Urea accumulated in excess around the peptide, to which it formed long-lived hydrogen bonds. The unfolding mechanisms induced by thermal denaturation and by urea are of a different nature, with urea-aqueous solutions providing a better peptide solvation than pure water. Our results suggest that the effect of urea on the chemical denaturation process involves both the direct and indirect mechanisms.