Choi Jun-Ho, Lee Hochan, Lee Kyung-Koo, Hahn Seungsoo, Cho Minhaeng
Department of Chemistry, Korea University, Seoul 136-701, Korea.
J Chem Phys. 2007 Jan 28;126(4):045102. doi: 10.1063/1.2424711.
Using the constrained molecular dynamics simulation method in combination with quantum chemistry calculation, Hessian matrix reconstruction, and fragmentation approximation methods, the authors have established computational schemes for numerical simulations of amide I IR absorption, vibrational circular dichroism (VCD), and two-dimensional (2D) IR photon echo spectra of the protein ubiquitin in water. Vibrational characteristic features of these spectra in the amide I vibration region are discussed. From the semiempirical quantum chemistry calculation results on an isolated ubiquitin, amide I local mode frequencies and vibrational coupling constants were fully determined. It turns out that the amide I local mode frequencies of ubiquitin in both gas phase and aqueous solution are highly heterogeneous and site dependent. To directly test the quantitative validity of thus obtained spectroscopic properties, they compared the experimentally measured amide I IR, 2D IR, and electronic circular dichroism spectra with experiments, and found good agreements between theory and experiments. However, the simulated VCD spectrum is just qualitatively similar to the experimentally measured one. This indicates that, due to delicate cancellations between the positive and negative VCD contributions, the prediction of protein VCD spectrum is critically relied on quantitative accuracy of the theoretical model for predicting amide I local mode frequencies. On the basis of the present comparative investigations, they found that the site dependency of amide I local mode frequency, i.e., diagonal heterogeneity of the vibrational Hamiltonian matrix in the amide I local mode basis, is important. It is believed that the present computational methods for simulating various vibrational and electronic spectra of proteins will be of use in further refining classical force fields and in addressing the structure-spectra relationships of proteins in solution.
作者采用约束分子动力学模拟方法，结合量子化学计算、海森矩阵重构和碎片化近似方法，建立了用于数值模拟水中蛋白质泛素的酰胺I红外吸收、振动圆二色性（VCD）和二维（2D）红外光子回波光谱的计算方案。讨论了这些光谱在酰胺I振动区域的振动特征。根据对孤立泛素的半经验量子化学计算结果，全面确定了酰胺I局部模式频率和振动耦合常数。结果表明，气相和水溶液中泛素的酰胺I局部模式频率高度不均匀且依赖于位点。为了直接检验由此获得的光谱性质的定量有效性，他们将实验测量的酰胺I红外、二维红外和电子圆二色光谱与实验进行了比较，发现理论与实验之间有很好的一致性。然而，模拟的VCD光谱仅在定性上与实验测量的光谱相似。这表明，由于VCD正负贡献之间的微妙抵消，蛋白质VCD光谱的预测严重依赖于预测酰胺I局部模式频率的理论模型的定量准确性。基于目前的比较研究，他们发现酰胺I局部模式频率的位点依赖性，即在酰胺I局部模式基下振动哈密顿矩阵的对角不均匀性，很重要。相信目前用于模拟蛋白质各种振动和电子光谱的计算方法将有助于进一步完善经典力场，并解决溶液中蛋白质的结构-光谱关系。
