Cimas A, Maitre P, Ohanessian G, Gaigeot M-P
Laboratoire Analyse et Modélisation pour la Biologie et l'Environnement, UMR8587 CNRS, Université d'Evry val d'Essonne, boulevard F. Mitterrand, Bat. Maupertuis, 91025 Evry Cedex, France, Laboratoire de Chimie Physique, Université Paris Sud 11, UMR8000 CNRS, Faculté des sciences, bâtiment 350, 91405 Orsay Cedex, France, and Laboratoire des Mécanismes réactionnels, Département de Chimie, Ecole Polytechnique, CNRS, 91128 Palaiseau Cedex, France.
J Chem Theory Comput. 2009 Sep 8;5(9):2388-400. doi: 10.1021/ct900179d.
The local structure of phosphorylated residues in peptides and proteins may have a decisive role on their functional properties. Recent IRMPD experiments have started to provide spectroscopic signatures of such structural details; however, a proper modeling of these signatures beyond the harmonic approximation, taking into account temperature and entropic effects, is still lacking. In order to bridge this gap, DFT-based Car-Parrinello molecular dynamics simulations have been carried out for the first time on a phosphorylated amino acid, gaseous deprotonated phosphoserine. It is found that all vibrational signatures are successfully reproduced, and new deconvolution techniques enable the assignment of the vibrational spectrum directly from the dynamics results and the comparison of vibrational modes at several temperatures. The lowest energy structure is found to involve a strong hydrogen bond between the deprotonated phosphate and the acid with relatively small free energy barriers to proton transfer; however, we find that proton shuttling between the two sites does not occur frequently. Anharmonicities turn out to be important to reproduce the frequencies and shapes of several experimental bands. Comparison of room temperature and 13 K, effectively harmonic dynamics, allows insight to be obtained into vibrational anharmonicities. In particular, a significant blue-shift and broadening of the C═O stretching frequency from 13 to 300 K can be ascribed to intrinsic anharmonicity rather than to anharmonic coupling to other modes. On the other hand, significant couplings are found for the stretching motions of the hydrogen bonded P-O bond and of the free P-OH bond, mainly with modes within the phosphate group.
肽和蛋白质中磷酸化残基的局部结构可能对其功能特性起决定性作用。最近的红外多光子解离（IRMPD）实验已开始提供此类结构细节的光谱特征；然而，仍缺乏在考虑温度和熵效应的情况下，超越简谐近似对这些特征进行恰当建模的方法。为了弥补这一差距，首次对磷酸化氨基酸气态去质子化磷酸丝氨酸进行了基于密度泛函理论（DFT）的Car-Parrinello分子动力学模拟。结果发现，所有振动特征均能成功再现，并且新的去卷积技术能够直接根据动力学结果对振动光谱进行归属，并比较几个温度下的振动模式。发现能量最低的结构涉及去质子化磷酸盐与酸之间的强氢键，质子转移的自由能垒相对较小；然而，我们发现两个位点之间的质子穿梭并不频繁。结果表明，非谐性对于再现几个实验谱带的频率和形状很重要。比较室温与13 K（有效简谐动力学），有助于深入了解振动非谐性。特别是，从13 K到300 K，C═O伸缩频率的显著蓝移和展宽可归因于内在非谐性，而非与其他模式的非谐耦合。另一方面，发现氢键合的P-O键和游离P-OH键的伸缩运动存在显著耦合，主要与磷酸基团内的模式耦合。
