Modeling of biomolecular machines in non-equilibrium steady states

Numerical computations have become a pillar of all modern quantitativesciences. Any computation involves modeling--even if often this step is notmade explicit--and any model has to neglect details while still beingphysically accurate. Equilibrium statistical mechanics guides both thedevelopment of models and numerical methods for dynamics obeying detailedbalance. For systems driven away from thermal equilibrium such a universaltheoretical framework is missing. For a restricted class of driven systemsgoverned by Markov dynamics and local detailed balance, stochasticthermodynamics has evolved to fill this gap and to provide fundamentalconstraints and guiding principles. The next step is to advance stochasticthermodynamics from simple model systems to complex systems with ten thousandsor even millions degrees of freedom. Biomolecules operating in the presence ofchemical gradients and mechanical forces are a prime example for thischallenge. In this Perspective, we give an introduction to isothermalstochastic thermodynamics geared towards the systematic multiscale modeling ofthe conformational dynamics of biomolecular and synthetic machines, and weoutline some of the open challenges.