Mutter Shaun T, Zielinski François, Cheeseman James R, Johannessen Christian, Popelier Paul L A, Blanch Ewan W
Manchester Institute of Biotechnology and Faculty of Life Sciences, University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.
Phys Chem Chem Phys. 2015 Feb 28;17(8):6016-27. doi: 10.1039/c4cp05517a.
As two biologically and medically relevant monosaccharides, the constituents of hyaluronic acid, d-glucuronic acid and N-acetyl-d-glucosamine, constitute perfect test cases for the development of carbohydrate-specific structural methods. These two molecules have been analysed by Raman optical activity (ROA), a spectroscopic technique exhibiting exquisite sensitivity to stereochemistry. We show that it is possible to support the experiment with a simulation approach combining density functional theory (DFT) and molecular dynamics (MD), both using explicit solvation. Thus, we have gained new insight into the crucial hydration effects that contribute to the conformational dynamics of carbohydrates and managed to characterize in detail the poorly understood vibrational nature of this class of biomolecules. Experimental and calculated ROA spectra of these two molecules are reported and excellent agreement has been found. More specifically, comparison has been made with the more commonly used gas phase and implicitly solvated calculation approaches, which offer poor or zero modelling of solvent interactions. The calculated spectra have been used to resolve the structural origins of the observed bands, a current challenge in the study of carbohydrates due to a lack of definitive vibrational assignments. We report and analyse major features in the fingerprint region of the ROA spectra, with recurrent structural and spectral features between the two monosaccharides observed.
作为两种具有生物学和医学相关性的单糖，透明质酸的组成成分——D-葡萄糖醛酸和N-乙酰-D-葡萄糖胺，构成了开发碳水化合物特异性结构方法的完美测试案例。这两种分子已通过拉曼光学活性（ROA）进行了分析，ROA是一种对立体化学表现出极高灵敏度的光谱技术。我们表明，可以用一种结合密度泛函理论（DFT）和分子动力学（MD）的模拟方法来辅助实验，二者均使用显式溶剂化。因此，我们对有助于碳水化合物构象动力学的关键水合作用有了新的认识，并成功详细表征了这类生物分子鲜为人知的振动性质。报告了这两种分子的实验和计算得到的ROA光谱，发现二者吻合度很高。更具体地说，与更常用的气相和隐式溶剂化计算方法进行了比较，后两种方法对溶剂相互作用的建模效果很差或为零。计算得到的光谱已用于解析观察到的谱带的结构起源，由于缺乏明确的振动归属，这是碳水化合物研究中的一个当前挑战。我们报告并分析了ROA光谱指纹区的主要特征，观察到这两种单糖之间存在反复出现的结构和光谱特征。
