Stressing disulfide bonds! Nucleophilic thiol-disulfide exchange reactions within the I27 domain of titin were previously investigated with force clamp AFM. Here, all possible pathways associated with disulfide bond scission at constant tensile force are revealed in terms of end-to-end distances by using force clamp molecular dynamics. The simulations, together with experimental data unravel the competition between mechanochemical bond activation and solvent-mediated regiospecificity exhibited during SS bond cleavage due to the nucleophilic substitution mechanism within a stretched peptide.