Abstract
In protein environments, proton transfer reactions occur along polar or charged residues and isolated water molecules. These species consist of H-bond networks that serve as proton transfer pathways; therefore, thorough understanding of H-bond energetics is essential when investigating proton transfer reactions in protein environments. When the pKa values (or proton affinity) of the H-bond donor and acceptor moieties are equal, significantly short, symmetric H-bonds can be formed between the two, and proton transfer reactions can occur in an efficient manner. However, such short, symmetric H-bonds are not necessarily stable when they are situated near the protein bulk surface, because the condition of matching pKa values is opposite to that required for the formation of strong salt bridges, which play a key role in protein-protein interactions. To satisfy the pKa matching condition and allow for proton transfer reactions, proteins often adjust the pKa via electron transfer reactions or H-bond pattern changes. In particular, when a symmetric H-bond is formed near the protein bulk surface as a result of one of these phenomena, its instability often results in breakage, leading to large changes in protein conformation.