  We present a simple and robust technique to extract kinetic rate models and
thermodynamic quantities from single molecule time traces. SMACKS (Single
Molecule Analysis of Complex Kinetic Sequences) is a maximum likelihood
approach that works equally well for long trajectories as for a set of short
ones. It resolves all statistically relevant rates and also their
uncertainties. This is achieved by optimizing one global kinetic model based on
the complete dataset, while allowing for experimental variations between
individual trajectories. In particular, neither a priori models nor equilibrium
have to be assumed. The power of SMACKS is demonstrated on the kinetics of the
multi-domain protein Hsp90 measured by smFRET (single molecule F\"orster
resonance energy transfer). Experiments in and out of equilibrium are analyzed
and compared to simulations, shedding new light on the role of Hsp90's ATPase
function. SMACKS pushes the boundaries of single molecule kinetics far beyond
current methods.
