Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
Phys Chem Chem Phys. 2011 Apr 14;13(14):6517-30. doi: 10.1039/c0cp02559c. Epub 2011 Mar 2.
The role of noncovalent interactions in carbohydrate recognition by aromatic amino acids has long been reported. To develop a molecular understanding of noncovalent interactions in the recognition process, we have examined a series of binary complexes between 3-methylindole (3-MeIn) and sugars. In particular, the geometries and binding affinities of 3-MeIn with α/β-D-glucose, β-D-galactose, α-D-mannose and α/β-L-fucose are obtained using the MP2(full)/6-31G(d,p) and the M06/TZV2D//MP2/6-31G(d,p) level of theories. The conventional hydrogen bonding such as N-H···O and C-H···O as well as nonconventional O-H···π and C-H···π type of interactions is, in general, identified as responsible for the moderately strong interaction energies. Large variations in the position-orientations of 3-MeIn with respect to saccharide are noticed, within the same sugar family, as well as across different sugar series. Furthermore, complexes with large differences in their geometries are recognized as capable of exhibiting very similar interaction energies, underscoring the significance of exhaustive conformation sampling, as carried out in the present study. These observations are readily attributed to the differences in the efficiency of the type of interactions enlisted above. The highest and lowest interaction energies, upon inclusion of 50% BSSE correction, are found to be -16.02 and -6.22 kcal mol(-1), respectively, for α-D-glucose (1a) and α-L-fucose (5j). While more number of prominent conventional hydrogen bonding contacts remains as a characteristic feature of the strongly bound complexes, the lower end of the interaction energy spectrum is dominated by multiple C-H···π interactions. The complexes exhibiting as many as four C-H···π contacts are identified in the case of α/β-D-glucose, β-D-galactose, and α/β-L-fucose with an interaction energy hovering around -8 kcal mol(-1). The presence of effective C-H···π interactions is found to be dependent on the saccharide configuration as well as the area of the apolar patch constituted by the C-H groups. The study offers a comprehensive set of binary complexes, across different saccharides, which serves as an illustration of the significance and ubiquitous nature of C-H···π interactions in carbohydrate binding in saccharide-protein complexes.
非共价相互作用在芳香族氨基酸识别碳水化合物中的作用早已得到报道。为了从分子水平上理解识别过程中非共价相互作用，我们研究了一系列 3-甲基吲哚（3-MeIn）与糖之间的二元复合物。特别是，使用 MP2(full)/6-31G(d,p)和 M06/TZV2D//MP2/6-31G(d,p)理论水平，获得了 3-MeIn 与α/β-D-葡萄糖、β-D-半乳糖、α-D-甘露糖和α/β-L-岩藻糖的几何形状和结合亲和力。通常认为，氢键如 N-H···O 和 C-H···O 以及非氢键 O-H···π 和 C-H···π 类型的相互作用负责中等强度的相互作用能。在同一糖家族内以及不同糖系列之间，注意到 3-MeIn 相对于糖的位置取向有很大变化。此外，还发现几何形状差异很大的复合物能够表现出非常相似的相互作用能，这强调了在本研究中进行详尽构象采样的重要性。这些观察结果很容易归因于上述相互作用类型的效率差异。在包括 50%BSSE 校正后，发现α-D-葡萄糖（1a）和α-L-岩藻糖（5j）的最高和最低相互作用能分别为-16.02 和-6.22 kcal/mol。虽然具有更多数量的显著常规氢键接触仍然是强结合复合物的特征，但相互作用能谱的低端由多个 C-H···π 相互作用主导。在α/β-D-葡萄糖、β-D-半乳糖和α/β-L-岩藻糖的情况下，发现具有多达四个 C-H···π 接触的复合物，其相互作用能在-8 kcal/mol 左右。发现有效的 C-H···π 相互作用取决于糖的构型以及由 C-H 基团构成的非极性区域的面积。该研究提供了一套全面的二元复合物，涵盖了不同的糖，这说明了 C-H···π 相互作用在糖蛋白复合物中碳水化合物结合中的重要性和普遍性。
