Terreux R, Domard M, Viton C, Domard A
Laboratoire de Chimie Physique et de Modélisation Moléculaire, Faculté de Pharmacie, Université Claude Bernard, Lyon 1, 8 Avenue Rockefeller, 69373 Lyon Cedex 08, France.
Biomacromolecules. 2006 Jan;7(1):31-7. doi: 10.1021/bm0504126.
Molecular modeling is particularly useful to understand interactions between various kinds of molecules and ions. This study is aimed at studying the interactions between one Cu(2+) ion and one or several glucosamine residues. The geometries and the interaction energies of all of the complexes involving all of the dimers obtained from glucosamine and N-acetylglucosamine were computed by means of density functional theory (DFT) methods. In a first step, for the two dimers A-A and A-B (A for glucosamine and B for N-acetyl glucosamine), a starting geometry was built, and the energies were calculated using a rigid rotation of 30 degrees intervals for each of the dihedral angles (Phi and Psi) of the glycosidic bond, spanning the whole angular range. These calculations allowed us to retrieve the minimal energy conformation and investigate all possible conformations. The results were compared to some experimental data. In a second step, we investigated the interactions of Cu(2+) with the different possible coordination sites of A. For all complexes considered, the Cu(2+) site was completed with H(2)O and/or OH(-) ligands to have a global neutral charge. The calculations confirmed that the most stable interactions involved the free amino site in a "pending complex". Another pending form was possible considering the participation of the heterocyclic O site, but the latter was less favored. On the other hand, we also showed that glucosamine could not act as a bidentate ligand and that N-acetyl glucosamine was not coordinating with Cu(2+). Finally, our results evidenced a cooperative fixation of Cu(2+) ions when considering the complexation of two successive metal ions on the two consecutive glucosamine residues of the dimer A-A.
分子建模对于理解各种分子和离子之间的相互作用特别有用。本研究旨在研究一个Cu(2+)离子与一个或几个葡糖胺残基之间的相互作用。通过密度泛函理论(DFT)方法计算了所有由葡糖胺和N-乙酰葡糖胺得到的二聚体所涉及的配合物的几何结构和相互作用能。第一步，对于两个二聚体A-A和A-B（A代表葡糖胺，B代表N-乙酰葡糖胺），构建了起始几何结构，并使用糖苷键的每个二面角（Phi和Psi）以30度间隔的刚性旋转来计算能量，涵盖整个角度范围。这些计算使我们能够获得最低能量构象并研究所有可能的构象。将结果与一些实验数据进行了比较。第二步，我们研究了Cu(2+)与A的不同可能配位位点的相互作用。对于所有考虑的配合物，Cu(2+)位点用H(2)O和/或OH(-)配体完成以具有整体中性电荷。计算证实，最稳定的相互作用涉及“悬垂配合物”中的游离氨基位点。考虑到杂环O位点的参与，另一种悬垂形式也是可能的，但后者不太有利。另一方面，我们还表明葡糖胺不能作为双齿配体，并且N-乙酰葡糖胺不与Cu(2+)配位。最后，我们的结果证明了在考虑两个连续的金属离子在二聚体A-A的两个连续葡糖胺残基上的络合时，Cu(2+)离子的协同固定作用。
