Department of Biomedical Sciences, Creighton University, Omaha, Nebraska 68178, USA.
J Phys Chem B. 2010 Mar 4;114(8):3028-37. doi: 10.1021/jp910465e.
Molecular dynamics simulations of a beta-hairpin miniprotein, CLN025, were performed to examine the conformational stability of the peptide in H(2)O at 278, 300, 333, and 363 K, as well as in TFE, MeOH, and DMSO at 300 K. CLN025 is a variant of the Chignolin miniprotein, in which the terminal Gly residues of Chignolin are replaced with Tyr residues, which leads to a 29.7 K increase in melting temperature. The energy of the intramolecular interactions was calculated using DFT quantum chemical calculations at the BHandHLYP/cc-pVTZ level of theory. CLN025 maintained a beta-hairpin conformation in all environments. The beta-hairpin is stabilized by hydrogen bonds, an electrostatic interaction between the charged termini of the peptide, and weakly polar interactions. The interaction between the backbones of the N and C-terminal strands accounts for -97.32 to -120.87 kcal mol(-1) of the stabilization energy. The energies of the CH-pi interactions between Tyr2 and Pro4 were between -1.80 and -8.9 kcal mol(-1), and the energy of the Tyr2-Trp9 Ar-Ar interaction was between -0.43 and -8.11 kcal mol(-1). Increasing temperature caused the Tyr2-Pro4 CH-pi and the Tyr2-Trp9 and Tyr2-Tyr10 Ar-Ar interactions to become less favorable, but the Tyr1-Trp9 interaction became more favorable and played an important role in stabilizing the beta-hairpin of CLN025 that resulted in the increased melting temperature. Weakly polar interactions play an important role in the structure and stability of CLN025 and other proteins.
采用分子动力学模拟方法研究了β发夹短肽 CLN025 在 278、300、333 和 363 K 下的 H2O 以及在 300 K 下的 TFE、MeOH 和 DMSO 中的构象稳定性。CLN025 是 Chignolin 短肽的变体，其中 Chignolin 的末端 Gly 残基被 Tyr 残基取代，导致其熔点升高 29.7 K。采用 DFT 量子化学计算方法在 BHandHLYP/cc-pVTZ 理论水平上计算了分子内相互作用能。CLN025 在所有环境中均保持β发夹构象。氢键、肽末端的静电相互作用和弱极性相互作用稳定了β发夹。N 和 C 末端链的骨架之间的相互作用占稳定能的-97.32 到-120.87 kcal/mol。Tyr2 与 Pro4 之间的 CH-π相互作用的能量在-1.80 到-8.9 kcal/mol 之间，Tyr2-Trp9 Ar-Ar 相互作用的能量在-0.43 到-8.11 kcal/mol 之间。温度升高导致 Tyr2-Pro4 CH-π和 Tyr2-Trp9 和 Tyr2-Tyr10 Ar-Ar 相互作用变得不利，但 Tyr1-Trp9 相互作用变得更有利，并在稳定 CLN025 的β发夹结构中发挥重要作用，导致其熔点升高。弱极性相互作用在 CLN025 和其他蛋白质的结构和稳定性中发挥重要作用。
