Li Wenfei, Qin Meng, Tie Zuoxiu, Wang Wei
National Laboratory of Solid State Microstructure, and Department of Physics, Nanjing University, Nanjing 210093, China.
Phys Rev E Stat Nonlin Soft Matter Phys. 2011 Oct;84(4 Pt 1):041933. doi: 10.1103/PhysRevE.84.041933. Epub 2011 Oct 28.
We investigated the effects of solvents on the intrinsic propensity of peptide backbone conformations based on molecular dynamics simulations. The results show that compared with pure water, aqueous urea decreases the helix propensity. In comparison, methanol decreases the polyproline II (PPII) propensity. Such a solvent dependence of the intrinsic propensity of the backbone conformation is correlated with the solvent dependence of the hydration of the backbone groups and the formation probability of the local intrapeptide hydrogen bonds. Aqueous urea which has low ability to stabilize the local intrapeptide hydrogen bonds disfavors the helical conformation. Whereas, methanol which has low ability to hydrate the backbone groups disfavors the polyproline II conformation. In addition, the solvent effects can be further modulated by the side chains of the peptides. The solvent effects of the intrinsic propensity of peptide backbone conformations observed in this work suggest that changing the intrinsic propensity of the protein backbone conformations can partly contribute to the solvent-induced protein structure and dynamics variations. These results will be useful in understanding the solvent dependence of the conformational distributions of the unfolded proteins or peptides (or intrinsically disordered proteins) in which the global tertiary interactions are less important than that in the well-folded proteins.
我们基于分子动力学模拟研究了溶剂对肽主链构象内在倾向的影响。结果表明，与纯水相比，尿素水溶液降低了螺旋倾向。相比之下，甲醇降低了多聚脯氨酸II（PPII）倾向。主链构象内在倾向的这种溶剂依赖性与主链基团水化的溶剂依赖性以及局部肽内氢键的形成概率相关。尿素水溶液稳定局部肽内氢键的能力较低，不利于螺旋构象。而甲醇水化主链基团的能力较低，不利于多聚脯氨酸II构象。此外，溶剂效应可通过肽的侧链进一步调节。在这项工作中观察到的肽主链构象内在倾向的溶剂效应表明，改变蛋白质主链构象的内在倾向可部分导致溶剂诱导的蛋白质结构和动力学变化。这些结果将有助于理解未折叠蛋白质或肽（或内在无序蛋白质）构象分布的溶剂依赖性，其中全局三级相互作用比折叠良好的蛋白质中的重要性要低。
