Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis, Greece.
PLoS One. 2010 Dec 20;5(12):e15290. doi: 10.1371/journal.pone.0015290.
Conventional wisdom has it that the presence of disordered regions in the three-dimensional structures of polypeptides not only does not contribute significantly to the thermodynamic stability of their folded state, but, on the contrary, that the presence of disorder leads to a decrease of the corresponding proteins' stability. We have performed extensive 3.4 µs long folding simulations (in explicit solvent and with full electrostatics) of an undecamer peptide of experimentally known helical structure, both with and without its disordered (four residue long) C-terminal tail. Our simulations clearly indicate that the presence of the apparently disordered (in structural terms) C-terminal tail, increases the thermodynamic stability of the peptide's folded (helical) state. These results show that at least for the case of relatively short peptides, the interplay between thermodynamic stability and the apparent structural stability can be rather subtle, with even disordered regions contributing significantly to the stability of the folded state. Our results have clear implications for the understanding of peptide energetics and the design of foldable peptides.
传统观点认为，多肽三维结构中无序区域的存在不仅不会显著增加其折叠态的热力学稳定性，反而会导致相应蛋白质稳定性的降低。我们对一个具有实验已知螺旋结构的十一肽进行了长达 3.4 微秒的折叠模拟（在显式溶剂和完整静电场中），包括有无其无序（四个残基长）的 C 端尾部。我们的模拟清楚地表明，显然无序的（在结构上）C 端尾部的存在增加了肽折叠（螺旋）态的热力学稳定性。这些结果表明，至少对于相对较短的肽，热力学稳定性和明显的结构稳定性之间的相互作用可能非常微妙，即使是无序区域也会对折叠态的稳定性有显著贡献。我们的结果对理解肽能学和可折叠肽的设计具有明确的意义。
