Daura X, van Gunsteren W F, Mark A E
Laboratorium für Physikalische Chemie, ETH Zentrum, Zürich, Switzerland.
Proteins. 1999 Feb 15;34(3):269-80. doi: 10.1002/(sici)1097-0134(19990215)34:3<269::aid-prot1>3.0.co;2-3.
The thermodynamics of folding and unfolding of a beta-heptapeptide in methanol solution has been studied at four different temperatures, 298 K, 340 K, 350 K, and 360 K, by molecular dynamics simulation. At each of these temperatures, the 50-ns simulations were sufficient to generate an equilibrium distribution between a relatively small number of conformations (approximately 10(2)), showing that, even above the melting temperature (approximately 340 K), the peptide does not randomly sample conformational space. The free energy of folding and the free energy difference between pairs of conformations have been calculated from their relative populations. The experimentally determined folded conformation at 298 K, a left-handed 3(1)-helix, is at each of the four temperatures the predominant conformation, with its probability and average lifetime decreasing with increasing temperature. The most common intermediates of folding and unfolding are also the same at the four temperatures. Paths and rates of interconversion between different conformations have been determined. It has been found that folding can occur through multiple pathways, not necessarily downhill in free energy, although the final step involves a reduced number of intermediates.
通过分子动力学模拟，研究了一种β-七肽在甲醇溶液中于298 K、340 K、350 K和360 K这四个不同温度下折叠与解折叠的热力学性质。在每个温度下，50纳秒的模拟足以在相对少量的构象（约10²个）之间产生平衡分布，这表明即使在高于熔化温度（约340 K）时，该肽也不会随机采样构象空间。折叠的自由能以及构象对之间的自由能差已根据它们的相对丰度计算得出。实验确定的298 K时的折叠构象，即左手3(1)-螺旋，在这四个温度下均为主要构象，其概率和平均寿命随温度升高而降低。折叠和解折叠最常见的中间体在这四个温度下也相同。已确定了不同构象之间的相互转化途径和速率。已发现折叠可以通过多种途径发生，不一定是自由能下降的过程，尽管最后一步涉及的中间体数量减少。
