title: A Protein Data Bank survey reveals shortening of intermolecular hydrogen bonds in ligand-protein complexes when a halogenated ligand is an H-bond donor.
abstract: 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.
authors.affiliation: Biophysics Department, Institute of Biochemistry and Biophysics PAS, Warszawa, Poland.
authors.forename: Jarosław
authors.initials: J
authors.lastname: Poznański
authors.affiliation: Centre for Monitoring and Analyses of Population Health Status, National Institute of Public Health - National Institute of Hygiene, Warszawa, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Poznańska
authors.affiliation: Institute of Biochemistry and Biophysics PAS, Warszawa, Poland.
authors.forename: David
authors.initials: D
authors.lastname: Shugar
mesh_terms: D003625:Data Collection; D030562:Databases, Protein; D054879:Halogenation; D006860:Hydrogen Bonding; D008024:Ligands; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D015203:Reproducibility of Results
chemical_list: D008024:Ligands; D011506:Proteins