Nature of structural inhomogeneities on folding a helix and their influence on spectral measurements
Nature of structural inhomogeneities on folding a helix and their influence on spectral measurements
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DOI：
10.1073/pnas.0402933101
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发表时间：
2004-06-22
影响因子：
11.1
通讯作者：
García, AE
中科院分区：
文献类型：
--
作者：
Gnanakaran, S;Hochstrasser, RM;García, AE
广泛的构象采样和振动耦合计算为含有螺旋折叠和未折叠状态分布的水溶液中酰胺单元的结构不均匀光谱提供了定量基础。加帽螺旋肽 AA(AAKAA)(3)AAY 的复制品交换分子动力学模拟是在一定温度范围内进行的，其中系统处于折叠和展开状态。该采样定义了一组集合，该集合表征了通过其螺旋含量分数识别的构型的构象变异性。计算内部和外部（与水）氢键的影响以及酰胺-I 模式之间的耦合作为温度和螺旋含量的函数。还计算端到端距离和耦合分布。与非溶剂化的谱带相比，在所有温度下都存在的溶剂氢键使酰胺-I 谱带向低频方向移动。当肽热变性时，酰胺-I 谱带会移向更高的频率，因为溶剂氢键的增加无法补偿内部（螺旋）氢键的损失。在较高温度下沿着螺旋的模式耦合均匀性的损失是众所周知的酰胺红外光谱的热展宽的原因。计算出的肽片段的不均匀性预测了同位素编辑的螺旋的实验特性。
Extensive conformational sampling and calculations of vibrational coupling provide a quantitative basis for the structurally inhomogeneous spectra of the amide unit in aqueous solutions containing folded and unfolded state distributions of helices. Replica exchange molecular dynamics simulations of the capped helical peptide, AA(AAKAA)(3)AAY, is carried out over a range of temperatures, where the system populates the folded and unfolded states. This sampling defines a set of ensembles that characterizes the conformational variability for configurations identified by their fraction of helical content. The effects of hydrogen bonding, both internal and external (with water), and the coupling between amide-I modes are computed as a function of temperature and helical content. End-to-end distance and coupling distributions are also computed. The solvent H-bonding, which is present at all temperatures, shifts the amide-I band toward lower frequency compared with the unsolvated band. Upon thermal denaturation of the peptide, the amide-I band shifts to higher frequency because the increase in solvent H-bonding fails to compensate for the loss in internal (helical) H-bonds. The loss of uniformity of the mode coupling along the helix at higher temperatures accounts for the well-known thermal broadening of the amide IR spectrum. The calculated inhomogeneities of segments of the peptide predict experimental properties of isotope-edited helices.