Low-barrier hydrogen bonds in proteins

Hydrogen bonding interactions are one of the most important chemical interactions among materials, especially biological materials, which help confer specificity, which is crucial for their efficient functioning. Recently, low-barrier hydrogen bonds (LBHBs) have been proposed to play a critical role in enzyme catalysis. In this review, tools to identify LBHBs are described, along with analyses of neutron crystal structures of small molecules to identify geometric parameters characteristic of LBHBs, which are assumed to be characterized by dynamic disorder along the hydrogen bond (H-bond) of the bonding hydrogen atom. The analysis of protein structures determined by neutron diffraction indicates that LBHBs are found to occur in both active site and non-active site regions of a protein. Moreover, very short H-bonds are observed in the vicinity of folding cores identified through nuclear magnetic resonance studies on two proteins, SUMO-1 and HIV-1 protease. This observation suggests that LBHBs may also be important in the context of folding of proteins.