Differential stability of the triple helix of (Pro-Pro-Gly)10 in H2O and D2O:: Thermodynamic and structural explanations
Differential stability of the triple helix of (Pro-Pro-Gly)10 in H2O and D2O:: Thermodynamic and structural explanations
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DOI：
10.1080/07391102.1999.10508379
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发表时间：
1999-12-01
影响因子：
4.4
通讯作者：
Bhatnagar, RS
中科院分区：
文献类型：
--
作者：
Gough, CA;Bhatnagar, RS
（Pro-Pro-Gly）（10）[（PPG（10））]是一种胶原蛋白样多肽，在略低于生理温度的水溶液中形成三螺旋聚脯氨酸-II结构，熔融温度为24.5 ℃。在这篇文章中，我们提出了圆二色光谱，证明了随着向（PPG）（10）的H2O溶液中加入增加量的D2 O，熔融温度增加，其中纯D2 O的熔融温度达到40 ℃。数据的热力学分析表明，这一结果是由于在D2 O相对于H2O中展开的增加的热力学。为了对这一结果提供理论解释，我们使用了我们先前开发的（PPG）（10）的水合模型，其中在空间拥挤的沃茨和肽键羰基之间形成链间水桥。能量最小化后，使用氢键参数的水，和改变的氢键参数，再现羰基氧-水氧距离的差异，发现在小分子晶体结构中含有有机分子和H2O或D2 O之间的氧-氧-氢键。发现使用再现氢键与D2 O的典型距离的氢键参数导致水合（PPG）的势能显著降低（10）。这种能量的降低涉及能量项，其仅与改变的氢键参数间接相关，因此不是人为的;内（PPG（10））能量，加上水（PPG（10））货车范德华能量（不包括氢键相互作用），降低到足以定性地解释三螺旋构象的较低焓，相对于未折叠状态，在D2 O和H2O中。这一结果表明，羰基-D2 O氢键的几何形状允许形成良好的氢键，而不会像在通过H2O水合的情况下那样从其他因素中做出尽可能多的能量牺牲。
(Pro-Pro-Gly)(10) [(PPG(10))], a collagen-like polypeptide, forms a triple-helical, polyproline-II structure in aqueous solution at temperatures somewhat lower than physiological, with a melting temperature of 24.5 degrees C. In this article, we present circular dichroism spectra that demonstrate an increase of the melting temperature with the addition of increasing amounts of D2O to an H2O solution of (PPG)(10), with the melting temperature reaching 40 degrees C in pure D2O. A thermodynamic analysis of the data demonstrates that this result is due to an increasing enthalphy of unfolding in D2O vs. H2O. To provide a theoretical explanation for this result, we have used a model for hydration of (PPG)(10) that we developed previously, in which inter-chain water bridges are formed between sterically crowded waters and peptide bond carbonyls. Energy minimizations were performed upon this model using hydrogen bond parameters for water, and altered hydrogen bond parameters that reproduced the differences in carbonyl oxygen-water oxygen distances found in small-molecule crystal structures containing oxygen-oxygen hydrogen bonds between organic molecules and H2O or D2O. It was found that using hydrogen bond parameters that reproduced the distance typical of hydrogen bonds to D2O resulted in a significant lowering of the potential energy of hydrated (PPG)(10). This lowering of the energy involved energetic terms that were only indirectly related to the altered hydrogen bond parameters, and were therefore not artifactual; the intra-(PPG(10)) energy, plus the water-(PPG(10)) van der Waals energy (not including hydrogen bond interactions), were lowered enough to qualitatively account for the lower enthalpy of the triple-helical conformation, relative to the unfolded state, in D2O vs. H2O. This result indicates that the geometry of the carbonyl-D2O hydrogen bonds allows formation of good hydrogen bonds without making as much of an energetic sacrifice from other factors as in the case of hydration by H2O.