Low-barrier hydrogen bonds (LBHBs) are a special type of short hydrogen bond (HB) that is characterized by the equal sharing of a hydrogen atom. The existence and catalytic role of LBHBs in proteins has been intensely contested. Advancements in X-ray and neutron diffraction methods has revealed delocalized hydrogen atoms involved in potential LBHBs in a number of proteins, while also demonstrating that short HBs are not necessarily LBHBs. More importantly, a series of experiments on ketosteroid isomerase (KSI) have suggested that LBHBs are significantly stronger than standard HBs in the protein microenvironment in terms of enthalpy, but not free energy. The discrepancy between the enthalpy and free energy of LBHBs offers clues to the challenges, and potential solutions, of the LBHB debate, where the unique strength of LBHBs plays a special role in the kinetic processes of enzyme function and structure, together with other molecular forces in a pre-organized environment.

低能垒氢键 (LBHB) 是一种特殊类型的短氢键 (HB)，其特征是平均共享一个氢原子。LBHBs 在蛋白质中的存在和催化作用一直备受争议。X 射线和中子衍射方法的进步揭示了许多蛋白质中潜在的 LBHBs 中涉及的离域氢原子，同时也证明了短 HBs 不一定是 LBHBs。更重要的是，一系列关于酮类固醇异构酶 (KSI) 的实验表明，LBHBs 在蛋白质微环境中在焓方面明显强于标准 HBs，但在自由能方面则不然。LBHB 的焓和自由能之间的差异为 LBHB 辩论的挑战和潜在解决方案提供了线索，