Atomistic evidence of how force dynamically regulates thiol/disulfide exchange.
The intricate coupling of mechanical force and chemical reactivity has been increasingly revealed in recent years by force spectroscopy experiments on the thiol/disulfide exchange reaction. We here aimed at elucidating the underlying dynamic effects of force on the reaction center for the case of disulfide bond reduction by dithiothreitol at forces of 200-2000 pN, by combining transition path sampling and quantum/classical mechanical simulations. Reaction rates and their dependence on force as quantified by Δx(r), the distance between reactant and transition state, are in good agreement with experiments but indicate a shift of the transition state structure at high forces. Indeed, while an associate S(N)2 mechanism prevails, force causes a move of the transition state to a longer length of the cleaving bond and a shorter length of the forming disulfide bond. Our results highlight the distribution of force into various degrees of freedom, which implies that care must be taken when correlating Δx(r) with a single order parameter of the reaction.
CAS-MPG Partner Institute and Key Laboratory for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
Wenjin
W
Li
Frauke
F
Gräter
D004220:Disulfides / Q000737:chemistry*; D004229:Dithiothreitol / Q000737:chemistry; D007700:Kinetics; D055595:Mechanical Phenomena; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013816:Thermodynamics
D004220:Disulfides; D013438:Sulfhydryl Compounds; D004229:Dithiothreitol