Protocol for Free Energy Estimates from Nonequilibrium Work Averages

5 Protocol for Free Energy Estimates from Nonequilibrium Work Averages 

Following is a schematic protocol summarizing the main steps in estimating free energies from nonequilibrium work averages. 

Create an equilibrium ensemble of starting configurations. To create N initial conformations representative of the equilibrium ensemble for Hamiltonian - // (z. A = 0), one can, for instance, save conformations at regular intervals during a long equilibrium simulation. In some cases, accelerated sampling procedures may be necessary. 

Determine the work distribution. After every time (or Monte Carlo) step during the simulations, change the Hamiltonian according to the prescribed path A (f) and accumulate the work performed as part of that change. Collect the work values from the N runs for analysis. 

Perform backward perturbation to improve accuracy. If possible, repeat the procedure starting from 34 z, A = 1). 

---