Lucas Xavier, Bauzá Antonio, Frontera Antonio, Quiñonero David
Pharmaceutical Bioinformatics , Institute of Pharmaceutical Sciences , Albert-Ludwigs-University , Hermann-Herder-Str. 9 , D-79104 Freiburg , Germany . Email:
Departament de Química , Universitat de les Illes Balears , Crta. de Valldemossa km 7.5 , 07122 Palma de Mallorca , Spain . Email:
Chem Sci. 2016 Feb 1;7(2):1038-1050. doi: 10.1039/c5sc01386k. Epub 2015 Jun 5.
Noncovalent interactions have a constitutive role in the science of intermolecular relationships, particularly those involving aromatic rings such as π-π and cation-π. In recent years, anion-π contact has also been recognized as a noncovalent bonding interaction with important implications in chemical processes. Yet, its involvement in biological processes has been scarcely reported. Herein we present a large-scale PDB analysis of the occurrence of anion-π interactions in proteins and nucleic acids. In addition we have gone a step further by considering the existence of cooperativity effects through the inclusion of a second noncovalent interaction, π-stacking, T-shaped, or cation-π interactions to form anion-π-π and anion-π-cation triads. The statistical analysis of the thousands of identified interactions reveals striking selectivities and subtle cooperativity effects among the anions, π-systems, and cations in a biological context. The reported results stress the importance of anion-π interactions and the cooperativity that arises from ternary contacts in key biological processes, such as protein folding and function and nucleic acids-protein and protein-protein recognition. We include examples of anion-π interactions and triads putatively involved in enzymatic catalysis, epigenetic gene regulation, antigen-antibody recognition, and protein dimerization.
非共价相互作用在分子间关系科学中具有重要作用，尤其是那些涉及芳香环的相互作用，如π-π相互作用和阳离子-π相互作用。近年来，阴离子-π相互作用也被认为是一种非共价键相互作用，在化学过程中具有重要意义。然而，其在生物过程中的参与情况鲜有报道。在此，我们对蛋白质和核酸中阴离子-π相互作用的出现情况进行了大规模的蛋白质数据银行（PDB）分析。此外，我们还进一步考虑了通过引入第二种非共价相互作用（π-堆积、T形或阳离子-π相互作用）形成阴离子-π-π和阴离子-π-阳离子三联体时协同效应的存在。对数千种已确定相互作用的统计分析揭示了在生物环境中阴离子、π体系和阳离子之间显著的选择性和微妙的协同效应。报道的结果强调了阴离子-π相互作用以及三元接触产生的协同效应在关键生物过程中的重要性，如蛋白质折叠与功能以及核酸-蛋白质和蛋白质-蛋白质识别。我们列举了可能参与酶催化、表观遗传基因调控、抗原-抗体识别和蛋白质二聚化的阴离子-π相互作用和三联体的例子。
