Department of Biomedical Engineering, Tufts University, Medford, Massachusetts.
Biophys J. 2013 Oct 1;105(7):1681-8. doi: 10.1016/j.bpj.2013.08.018.
The contribution of ionic interactions to the stability of the collagen triple helix was studied using molecular dynamics (MD) simulations and biophysical methods. To this end, we examined the stability of a host-guest collagen model peptide, Ac-GPOGPOGPYGXOGPOGPO-NH2, substituting KGE, KGD, EGK, and DGK for the YGX sequence. All-atom, implicit solvent MD simulations show that the fraction of cross-chain ionic interactions formed is different, with the most pronounced in the KGE and KGD sequences, and the least in the DGK sequence. To test whether the fraction of cross-chain ionic interactions correlates with the stability, experimental measurements of thermostability were done using differential scanning calorimetry and circular dichroism spectroscopy. It was found that the melting temperature is very similar for KGE and KGD peptides, whereas the EGK peptide has lower thermostability and the DGK peptide is the least thermostable. A novel, to our knowledge, computational protocol termed temperature-scan MD was applied to estimate the relative stabilities of the peptides from MD simulations. We found an excellent correlation between transition temperatures obtained from temperature-scan MD and those measured experimentally. These results suggest the importance of cross-chain ionic interactions for the stability of collagen triple helix and confirm the utility of MD simulations in predicting interactions and stability in this system.
本研究采用分子动力学（MD）模拟和生物物理方法研究了离子相互作用对胶原蛋白三螺旋稳定性的贡献。为此，我们研究了一种主体-客体胶原蛋白模型肽 Ac-GPOGPOGPYGXOGPOGPO-NH2 的稳定性，该模型肽将 YGX 序列中的 Y 替换为 KGE、KGD、EGK 和 DGK。全原子、隐溶剂 MD 模拟表明，形成的链间离子相互作用的比例不同，在 KGE 和 KGD 序列中最为明显，在 DGK 序列中最为不明显。为了测试链间离子相互作用的比例是否与稳定性相关，我们使用差示扫描量热法和圆二色光谱法进行了热稳定性的实验测量。结果发现，KGE 和 KGD 肽的熔点非常相似，而 EGK 肽的热稳定性较低，DGK 肽的热稳定性最低。应用了一种新颖的、据我们所知的计算方案，称为温度扫描 MD，以从 MD 模拟中估计肽的相对稳定性。我们发现，从温度扫描 MD 获得的转变温度与实验测量值之间存在极好的相关性。这些结果表明链间离子相互作用对胶原蛋白三螺旋稳定性的重要性，并证实了 MD 模拟在预测该体系中相互作用和稳定性方面的实用性。
