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Regulation of (Bio)chemical reactions by mechanical force has been proposed
to be fundamental to cellular functions[1,2,3]. Atomic force microscopy experiments
have identified the effect of mechanical force on the reactivity of thiol/disulfide
exchange, a biologically important reaction[4]. In order to understand the influence of
the force at an atomistic level, we have performed hybrid quantum mechanics -
molecular mechanics (QM/MM) transition path sampling simulation of the reaction
under external forces. The results of the simulations supported the experimental findings
and demonstrated that the location of the transition state on the free energy surface was
shifted due to force[5].
[1] Beyer MK, Clausen-Schaumann H. Chem. ReV. (2005) 105: 2921-2948.
[2] Bustamante C, Chemla Y, Forde N, Izhaky D. Annu. Rev. Biochem. (2004) 73: 705-748.
[3] Vogel V, Sheetz M. Nat. Rev. Mol. Cell Biol. (2006) 7: 265-275.
[4] Wiita AP, Ainavarapu SR, Huang HH, Fernandez JM. Proc.Natl. Acad. Sci. U.S.A. (2006) 103:
7222-7227.
[5] Li W, Graeter F. J. Amer. Chem. Soc. (2010) 132: 16790-5.
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