Dipartimento di Chimica Fisica ed Elettrochimica and INSTM UdR, Università degli Studi di Milano, Via Golgi 19, 20133, Milano, Italy.
Phys Chem Chem Phys. 2011 Nov 21;13(43):19508-16. doi: 10.1039/c1cp22436k. Epub 2011 Sep 30.
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.
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。许多药物是卤化分子，最近已经表明许多卤化配体与生物分子形成卤键。由于卤键的性质是由于卤素原子周围的静电势各向异性引起的，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键。我们表明，在卤素原子上引入伪原子可以使我们正确描述静电势的各向异性，并对蛋白质与卤化配体的复合物进行分子动力学模拟，从而再现实验值。结果与晶体学数据和混合量子力学/分子力学计算进行了比较。
