Creamer T P, Rose G D
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Protein Sci. 1995 Jul;4(7):1305-14. doi: 10.1002/pro.5560040706.
The thermodynamic basis of helix stability in peptides and proteins is a topic of considerable interest. Accordingly, we have computed the interactions between side chains of all hydrophobic residue pairs and selected triples in a model helix, using Boltzmann-weighted exhaustive modeling. Specifically, all possible pairs from the set Ala, Cys, His, Ile, Leu, Met, Phe, Trp, Tyr, and Val were modeled at spacings of (i, i + 2), (i, i + 3), and (i, i + 4) in the central turn of a model poly-alanyl alpha-helix. Significant interactions--both stabilizing and destabilizing-- were found to occur at spacings of (i, i + 3) and (i, i + 4), particularly in side chains with rings (i.e., Phe, Tyr, Trp, and His). In addition, modeling of leucine triples in a helix showed that the free energy can exceed the sum of pairwise interactions in certain cases. Our calculated interaction values both rationalize recent experimental data and provide previously unavailable estimates of the constituent energies and entropies of interaction.
肽和蛋白质中螺旋稳定性的热力学基础是一个备受关注的话题。因此，我们使用玻尔兹曼加权穷举建模法，计算了模型螺旋中所有疏水残基对和选定三元组侧链之间的相互作用。具体而言，在模型聚丙氨酰α-螺旋的中心转角处，对丙氨酸、半胱氨酸、组氨酸、异亮氨酸、亮氨酸、甲硫氨酸、苯丙氨酸、色氨酸、酪氨酸和缬氨酸集合中的所有可能对，以(i, i + 2)、(i, i + 3)和(i, i + 4)的间距进行建模。发现在(i, i + 3)和(i, i + 4)的间距处会发生显著的相互作用，既有稳定作用也有去稳定作用，特别是在带有环的侧链（即苯丙氨酸、酪氨酸、色氨酸和组氨酸）中。此外，对螺旋中亮氨酸三元组的建模表明，在某些情况下自由能可能超过成对相互作用的总和。我们计算得到的相互作用值既使最近的实验数据合理化，又提供了此前无法获得的组成能量和相互作用熵的估计值。
