CPMD simulation of a bimolecular chemical reaction: Nucleophilic attack of a disulfide bond under mechanical stress

Previous single-molecule atomic force microscopy (AFM) experiments showed a change in the reactivity of a bimolecular substitution reaction with a definite force acting on a protein containing disulfide bonds. Using Car-Parrinello molecular dynamics (CPMD) simulations, we analyse the relevant reaction pathways for the breaking of a disulfide bond in the presence of nucleophiles. Breaking disulfide bonds: Disulfide bonds are destabilized by steric or mechanical strain. In a basic environment, they may be broken through nucleophilic attack. Car-Parrinello molecular dynamics (CPMD) simulations allow the analysis of the mechanism of this reaction and of side reactions for comparison with AFM experiments (see figure).