Theory of rapid force spectroscopy

In dynamic force spectroscopy, single (bio-)molecular bonds are actively broken to assess their range and strength. At low loading rates, the experimentally measured statistical distributions of rupture forces can be analysed using Kramers’ theory of spontaneous unbinding. The essentially deterministic unbinding events induced by the extreme forces employed to speed up full-scale molecular simulations have been interpreted in mechanical terms, instead. Here we start from a rigorous probabilistic model of bond dynamics to develop a unified systematic theory that provides exact closed-form expressions for the rupture force distributions and mean unbinding forces, for slow and fast loading protocols. Comparing them with Brownian dynamics simulations, we find them to work well also at intermediate pulling forces. This renders them an ideal companion to Bayesian methods of data analysis, yielding an accurate tool for analysing and comparing force spectroscopy data from a wide range of experiments and simulations. Dynamic force spectroscopy is widely applied to probe molecular interactions by forcible bond breaking, but it currently lacks an analytical theory that spans the divide between experiment and simulation. Here, such a unified framework is developed and shown to be accurate for slow and fast loading.