Abstract
Recent force microscopy measurements on the mechanically activated cleavage of a protein disulfide bond through reaction with hydroxide ions revealed that for forces greater than 0.5 nN, the acceleration of the reaction rate is substantially reduced. Here, using ab initio simulations, we trace this 'reactivity switch' back to a dual role played by the mechanical force, which leads to antagonistic effects. On the one hand, the force performs work on the system, and thereby accelerates the reaction. On the other hand, the force also induces a conformational distortion that involves the S-S-C-C dihedral angle, which drives the disulfide into a conformation that is shielded against nucleophilic attack because of steric hindrance. The discovery of force-induced conformational changes that steer chemical reactivity provides a new key concept that is expected to be relevant beyond this specific case, for example in understanding how 'disulfide switches' regulate protein function and for the rational design of mechanoresponsive materials.
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