The gradient can be obtained by differentiating the estimator, and be fed to an external optimizer (e.g., optax 28 or jaxopt ) to update the force field parameters. A typical automatic workflow for a thermodynamic fitting using the reweighting MBAR estimator is given in Figure . In summary, for model optimization, DMFF currently supports a variety of object func-tions including energies, forces, ensemble averaged properties, and free energy differences.