Regulation of protein-ligand binding affinity by hydrogen bond pairing

Hydrogen (H)-bonds potentiate diverse cellular functions by facilitating molecular interactions. The mechanism and the extent to which H-bonds regulate molecular interactions are a largely unresolved problem in biology because the H-bonding process continuously competes with bulk water. This interference may significantly alter our understanding of molecular function, for example, in the elucidation of the origin of enzymatic catalytic power. We advance this concept by showing that H-bonds regulate molecular interactions via a hitherto unappreciated donor-acceptor pairing mechanism that minimizes competition with water. On the basis of theoretical and experimental correlations between H-bond pairings and their…

• NN
  National Natural Science Foundation of China

  Awards: 21473041, ID0EZZBG5293
• NI
  National Institute of Allergy and Infectious Diseases

  Awards: RO1AI100914, ID0EXYBG5291
• NI
  National Institute of Diabetes and Digestive and Kidney Diseases

  Awards: DK56338, ID0EIZBG5292