A differential fluctuation theorem

We derive a nonequil. thermodn. identity (the "differential fluctuation theorem") that connects forward and reverse joint probabilities of nonequil. work and of arbitrary generalized coordinates corresponding to states of interest. This identity allows us to est. the free energy difference between domains of these states. Our results follow from a general symmetry relation between avs. over nonequil. forward and backward path functions derived by Crooks (Crooks, G. E. 2000)​. We show how several existing nonequil. thermodn. identities can be obtained directly from the differential fluctuation theorem. We devise an approach for measuring conformational free energy differences, and we demonstrate its applicability to the anal. of mol. dynamics simulations by estg. the free energy difference between two conformers of the alanine dipeptide model system. We anticipate that these developments can be applied to the anal. of lab. expts.