Poznański Jarosław, Poznańska Anna, Shugar David
Biophysics Department, Institute of Biochemistry and Biophysics PAS, Warszawa, Poland.
Centre for Monitoring and Analyses of Population Health Status, National Institute of Public Health - National Institute of Hygiene, Warszawa, Poland.
PLoS One. 2014 Jun 16;9(6):e99984. doi: 10.1371/journal.pone.0099984. eCollection 2014.
Halogen bonding in ligand-protein complexes is currently widely exploited, e.g. in drug design or supramolecular chemistry. But little attention has been directed to other effects that may result from replacement of a hydrogen by a strongly electronegative halogen. Analysis of almost 30000 hydrogen bonds between protein and ligand demonstrates that the length of a hydrogen bond depends on the type of donor-acceptor pair. Interestingly, lengths of hydrogen bonds between a protein and a halogenated ligand are visibly shorter than those estimated for the same family of proteins in complexes with non-halogenated ligands. Taking into account the effect of halogenation on hydrogen bonding is thus important when evaluating structural and/or energetic parameters of ligand-protein complexes. All these observations are consistent with the concept that halogenation increases the acidity of the proximal amino/imino/hydroxyl groups and thus makes them better, i.e. stronger, H-bond donors.
目前，卤素键在配体 - 蛋白质复合物中得到了广泛应用，例如在药物设计或超分子化学领域。但是，对于由强电负性卤素取代氢原子可能产生的其他影响，人们关注较少。对近30000个蛋白质与配体之间氢键的分析表明，氢键的长度取决于供体 - 受体对的类型。有趣的是，蛋白质与卤化配体之间的氢键长度明显短于同一蛋白质家族与非卤化配体形成复合物时所估计的氢键长度。因此，在评估配体 - 蛋白质复合物的结构和/或能量参数时，考虑卤化对氢键的影响非常重要。所有这些观察结果都与以下概念一致：卤化会增加近端氨基/亚氨基/羟基的酸度，从而使其成为更好的，即更强的氢键供体。
