Challenges in Inferring the Directionality of Active Molecular Processes from Single-Molecule Fluorescence Resonance Energy Transfer Trajectories
Aljaž Godec, Dmitrii E. Makarov
Abstract
We discuss some of the practical challenges that one faces in using stochastic thermodynamics to infer directionality of molecular machines from experimental single-molecule trajectories. Because of the limited spatiotemporal resolution of single-molecule experiments and because both forward and backward transitions between the same pairs of states cannot always be detected, differentiating between the forward and backward directions of, e.g., an ATP-consuming molecular machine that operates periodically, turns out to be a nontrivial task. Using a simple extension of a Markov-state model that is commonly employed to analyze single-molecule transition-path measurements, we illustrate how irreversibility can be hidden from such measurements but in some cases can be uncovered when non-Markov effects in low-dimensional single-molecule trajectories are considered.