Time-Dependent Markov State Models for Single Molecule Force Spectroscopy.

This Letter demonstrates that using time-dependent Markov state models (TD-MSMs) one can obtain molecular-scale insights into force-extension curves for a variety of stretching experiments. A master-MSM constructed at a reference extension forms the basis for generating the required TD-MSM, i.e., the TD-MSM that is appropriate for the stretching experiment can be constructed from a single master-MSM. In addition, the availability of state-specific force models enable calculation of force-extension behavior in a variety of ensembles. Changes in the network topology upon stretching are related through a thermodynamic quantity termed the mechanical disposition. Proof-of-principle is provided using a stretched alanine decapeptide under a time-varying pulling force.

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