Effects of the biological backbone on stacking interactions at DNA-protein interfaces: the interplay between the backbone•••π and π•••π components
Effects of the biological backbone on stacking interactions at DNA-protein interfaces: the interplay between the backbone•••π and π•••π components
复制标题
DOI：
10.1039/c0cp00550a
复制
发表时间：
2010-11-01
影响因子：
3.3
通讯作者：
Wetmore, Stacey D.
中科院分区：
文献类型：
--
作者：
Churchill, Cassandra D. M.;Rutledge, Lesley R.;Wetmore, Stacey D.
先前比较了5个天然碱与芳香族氨基酸之间的(气相)MP2/6-31G*(0.25)pi中心点pi堆积作用，这些芳香氨基酸是由共轭环组成的(截断)单体和/或含有生物骨架(蛋白质骨架或脱氧核糖糖)的(扩展)单体计算的。虽然初步的能量结果表明蛋白质骨架增强，而脱氧核糖要么增强要么减弱，但使用截断模型计算的相互作用，这些影响的原因尚不清楚。本工作通过将扩展的络合物的相互作用能剖析为单个主干中心点pi和pi中心点pi分量来解释这些观察到的现象。我们的计算表明，扩展的络合物的总相互作用能可以预测为骨架中心点pi和pi中心点pi分量的总和，这表明生物骨架不会通过pi极化对环系统产生显著影响。相反，我们发现与截断二聚体相比，主链可以通过改变扩展二聚体中的相对环方向来间接影响圆周率中心点圆周率贡献的大小。此外，单个主干中心点pi的贡献强度被确定为显著的(高达18kJ摩尔(-1))。因此，模型扩展时能量变化的起源被发现是额外(有吸引力的)主干中心点pi分量和pi中心点pi相互作用强度的差异之间的平衡的结果。此外，为了了解自然界中生物骨架对DNA-蛋白质界面堆积相互作用的影响，我们分析了在选定的DNA-蛋白质晶体结构中发现的堆积相互作用，并验证了加法方法可以用来检验生物复合体中这些相互作用的强度。有趣的是，尽管分子中原子的量子理论(QTAIM)定性地证实了具有吸引力的主链中心点pi接触的存在，但QTAIM的电子密度分析无法定量地预测这些相互作用的相加关系。最重要的是，这项工作揭示了必须仔细考虑骨架中心点pi和pi中心点pi成分，以准确地确定DNA-蛋白质组装的整体稳定性。
The (gas-phase) MP2/6-31G*(0.25) pi center dot center dot center dot pi stacking interactions between the five natural bases and the aromatic amino acids calculated using (truncated) monomers composed of conjugated rings and/or (extended) monomers containing the biological backbone (either the protein backbone or deoxyribose sugar) were previously compared. Although preliminary energetic results indicated that the protein backbone strengthens, while the deoxyribose sugar either strengthens or weakens, the interaction calculated using truncated models, the reasons for these effects were unknown. The present work explains these observations by dissecting the interaction energy of the extended complexes into individual backbone center dot center dot center dot pi and pi center dot center dot center dot pi components. Our calculations reveal that the total interaction energy of the extended complex can be predicted as a sum of the backbone center dot center dot center dot pi and pi center dot center dot center dot pi components, which indicates that the biological backbone does not significantly affect the ring system through pi-polarization. Instead, we find that the backbone can indirectly affect the magnitude of the pi center dot center dot center dot pi contribution by changing the relative ring orientations in extended dimers compared with truncated dimers. Furthermore, the strengths of the individual backbone center dot center dot center dot pi contributions are determined to be significant (up to 18 kJ mol(-1)). Therefore, the origin of the energetic change upon model extension is found to result from a balance between an additional (attractive) backbone center dot center dot center dot pi component and differences in the strength of the pi center dot center dot center dot pi interaction. In addition, to understand the effects of the biological backbone on the stacking interactions at DNA-protein interfaces in nature, we analyzed the stacking interactions found in select DNA-protein crystal structures, and verified that an additive approach can be used to examine the strength of these interactions in biological complexes. Interestingly, although the presence of attractive backbone center dot center dot center dot pi contacts is qualitatively confirmed using the quantum theory of atoms in molecules (QTAIM), QTAIM electron density analysis is unable to quantitatively predict the additive relationship of these interactions. Most importantly, this work reveals that both the backbone center dot center dot center dot pi and pi center dot center dot center dot pi components must be carefully considered to accurately determine the overall stability of DNA-protein assemblies.