Base-catalyzed peptide hydrolysis is insensitive to mechanical stress.

摘要: Biochemical reactions can be guided by mechanical stress. An external force has been previously shown both experimentally and theoretically to act as a catalyst for the scission of disulfide bond in thiol/disulfide exchange reactions. How dynamics peptide hydrolysis, one most prevalent biochemical reactions, is influenced stretching was investigated here using combined quantum molecular (QM/MM) simulations together with transition path sampling. Our predict only marginally enhance reactivity rate-limiting step, nucleophilic attack hydroxide moiety, not alter reaction mechanism, even though its π-electron conjugation weakened force. We describe unidentified hydrogen bonded intermediate state, which likely play role general base-catalyzed analogous enzymatic predictions directly tested single molecule stretchi...