Reversible bond kinetics from single-molecule force spectroscopy experiments close to equilibrium

Analysis of bond rupture data from single-molecule force spectroscopy experiments commonly relies on the strong assumption that dissociation process is irreversible. However, with increased spatiotemporal resolution instruments it now possible to observe multiple unbinding-rebinding (or unfolding-refolding) events in a single pulling experiment. Here we augment theory force-induced unbinding by explicitly taking into account rebinding kinetics and provide approximate analytic solutions resulting rate equations. Furthermore, use short-time expansion exact construct numerically efficient maximum likelihood estimators for parameters force-dependent rates, which pair well complement established methods, such as analysis maps. The are independent applied protocol can therefore be used globally analyze force-extension traces both force-ramp force-clamp experiments. We an open-source implementation theory, evaluated Bell-like apply synthetic generated Gillespie stochastic simulation algorithm time-dependent rates.