Kinase inhibitors and the case for CH…O hydrogen bonds in protein–ligand binding

摘要: Although the hydrogen bond is known to be an important mediator of intermolecular interactions, there has yet analysis role CH...O bonds in protein-ligand complexes. In this work, we present evidence for such nonstandard from a survey aromatic ligands 184 kinase crystal structures and 358 high-resolution Protein Data Bank. CH groups adjacent positively charged nitrogen nicotinamide exhibit geometric preferences strongly suggestive bonding as do heterocyclic ligands, while other not these characteristics. Ab initio calculations reveal considerable range potentials among different ring systems, with heterocycles preferred inhibitors showing particularly favorable interactions. These results provide compelling existence well information on relative strength various donors. Such knowledge will value protein modeling, ligand design, structure-activity analysis.