  We introduce axiomatically a complete thermodynamic formalism for a single
macromolecule, either with or without detailed balance, in an isothermal
ambient fluid based on its stochastic dynamics. With detailed balance, the
novel theory yields mesoscopic, nonequilibrium generalizations for entropy and
free energy of the macromolecule. Mesoscopic energy and entropy fluctuate.
Expectation of entropy production equals zero if and only if the macromolecule
is at thermal equilibrium, in which we show entropy still fluctuates but free
energy is a constant. The entropy fluctuation a la L.D. Landau, precisely
matches the fluctuation in the internal energy, which in turn equals the
fluctuation in heat dissipation. As a generalization of Clausius' classic
result, the dynamic fluctuations in the entropy and energy of the macromolecule
are exactly compensated at thermal equilibrium. For systems with detailed
balance, Helmholtz free energy is shown to be the potential of Onsager's
thermodynamic force.
