Picosecond protein dynamics: the origin of the time-dependent spectral shift in the fluorescence of the single Trp in the protein GB1.
Picosecond protein dynamics: the origin of the time-dependent spectral shift in the fluorescence of the single Trp in the protein GB1.
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DOI：
10.1021/jp104425t
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发表时间：
2010-09
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影响因子：
--
通讯作者：
D. Toptygin;T. Woolf;L. Brand
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文献类型：
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作者：
D. Toptygin;T. Woolf;L. Brand
生物系统如何响应电荷移动是一个与生物功能直接相关的具有挑战性的问题。色氨酸残基的时间分辨荧光反映了蛋白质和溶剂对激发态和基态之间的pi电子密度差异的响应。在这项研究中，我们使用分子动力学计算了GB1蛋白中Trp-43荧光的随时间变化的光谱漂移(TDSS)。一种新的分离溶剂、蛋白质和荧光团对TDSS贡献的计算方法被应用于GB1在TIP3P水中的100个非平衡轨迹。结果支持了几个不平凡的结论。本体溶剂的纵向和横向驰豫模式都对蛋白质中的TDSS有贡献。所有慢于整体溶剂横向驰豫的松弛组分都有来自蛋白质和溶剂的显著贡献，且两者之间呈负相关。在GB1的TDSS中，五个指数项通过它们的松弛时间被很好地分开。0.036 pS项是由溶剂(60%)和蛋白质(40%)共同作用的。两个指数项分别代表TIP3P水的纵向(约=0.4ps)和横向(tau(D)约=5.6ps)弛豫模。131pS的项可归因于三级结构的微小变化，α-螺旋距离含有色氨酸-43的β链移动了0.2A。2580pS项是由于Glu-42侧链的构象变化，使其羧基接近激发的荧光团的正电荷末端。有趣的是，水抵消了这种构象变化导致的60%的TDSS。
How a biological system responds to a charge shift is a challenging question directly relevant to biological function. Time-resolved fluorescence of a tryptophan residue reflects protein and solvent response to the difference in pi-electron density between the excited and the ground state. In this study we use molecular dynamics to calculate the time-dependent spectral shift (TDSS) in the fluorescence of Trp-43 in GB1 protein. A new computational method for separating solvent, protein, and fluorophore contributions to TDSS is applied to 100 nonequilibrium trajectories for GB1 in TIP3P water. The results support several nontrivial conclusions. Both longitudinal and transverse relaxation modes of bulk solvent contribute to the TDSS in proteins. All relaxation components slower than the transverse relaxation of bulk solvent have significant contributions from both protein and solvent, with a negative correlation between them. Five exponential terms in the TDSS of GB1 are well separated by their relaxation times. A 0.036 ps term is due to both solvent (60%) and protein (40%). Two exponential terms represent longitudinal (tau(L) approximately = 0.4 ps) and transverse (tau(D) approximately = 5.6 ps) relaxation modes of TIP3P water. A 131 ps term is attributable to a small change in the tertiary structure, with the alpha-helix moving 0.2 A away from the beta-strand containing Trp-43. A 2580 ps term is due to the change in the conformation of the Glu-42 side chain that brings its carboxyl group close to the positively charged end of the excited fluorophore. Interestingly, water cancels 60% of the TDSS resulting from this conformational change.