Halogen bonding in ligand-receptor systems in the framework of classical force fields
Halogen bonding in ligand-receptor systems in the framework of classical force fields
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DOI：
10.1039/c1cp22436k
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发表时间：
2011-01-01
影响因子：
3.3
通讯作者：
Sironi, Maurizio
中科院分区：
文献类型：
--
作者：
Rendine, Stefano;Pieraccini, Stefano;Sironi, Maurizio
卤键是一种重要的非共价相互作用，在蛋白质-配体复合物的研究中受到越来越多的关注。许多药物是卤代分子，并且最近已经表明许多卤代配体与生物分子建立卤键。由于卤素键的性质是由于卤素原子周围的静电势的各向异性，因此不可能使用基于一组原子中心电荷的传统力场来研究生物分子中的卤素键。我们表明，引入伪原子的卤素使我们能够正确地描述静电势的各向异性，并进行分子动力学模拟与卤化配体的蛋白质复合物，重现实验值。晶体学数据和混合量子力学/分子力学计算的结果进行了比较。
Halogen bond is an important non-covalent interaction which is receiving a growing attention in the study of protein-ligand complexes. Many drugs are halogenated molecules and it has been recently shown that many halogenated ligands establish halogen bonds with biomolecules. As the halogen bond nature is due to an anisotropy of the electrostatic potential around halogen atoms, it is not possible to use traditional force fields based on a set of atom-centred charges to study halogen bonds in biomolecules. We show that the introduction of pseudo-atoms on halogens permits us to correctly describe the anisotropy of the electrostatic potential and to perform molecular dynamics simulations on complexes of proteins with halogenated ligands that reproduce experimental values. The results are compared with crystallographic data and with hybrid quantum mechanics/molecular mechanics calculations.