  Entropy and free-energy estimation are key in thermodynamic characterization
of simulated systems ranging from spin models through polymers, colloids,
protein structure, and drug-design. Current techniques suffer from being model
specific, requiring abundant computation resources and simulation at conditions
far from the studied realization. Here, we present a universal scheme to
calculate entropy using lossless compression algorithms and validate it on
simulated systems of increasing complexity. Our results show accurate entropy
values compared to benchmark calculations while being computationally
effective. In molecular-dynamics simulations of protein folding, we exhibit
unmatched detection capability of the folded states by measuring previously
undetectable entropy fluctuations along the simulation timeline. Such entropy
evaluation opens a new window onto the dynamics of complex systems and allows
efficient free-energy calculations.
