A Protein Data Bank survey reveals shortening of intermolecular hydrogen bonds in ligand-protein complexes when a halogenated ligand is an H-bond donor

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...

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Published inPloS one Vol. 9; no. 6; p. e99984
Main Authors Poznański, Jarosław, Poznańska, Anna, Shugar, David
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 16.06.2014
Public Library of Science (PLoS)
Subjects
Acidity
Biochemistry
Biology and Life Sciences
Biophysics
Bonding
Bonding strength
Bonds (Securities)
Chemical bonds
Chemistry
Coordination compounds
Data Collection
Databases, Protein
Deoxyribonucleic acid
DNA
Drug development
Electronegativity
Halogenated
Halogenation
Hydrogen
Hydrogen Bonding
Hydrogen bonds
Hydrogen ion concentration
Hydroxyl groups
Kinases
Ligands
Pharmaceutical sciences
Physical Sciences
Protein binding
Proteins
Proteins - chemistry
Proteins - metabolism
Random variables
Reproducibility of Results
RNA polymerase
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Summary: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.
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Competing Interests: The authors have declared that no competing interests exist.
Conceived and designed the experiments: JP DS. Analyzed the data: JP AP. Wrote the paper: JP AP DS.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0099984