Calculating free energy differences from raw alchemical data requires the use of some estimator. All estimators in alchemlyb conform to a common design pattern, with a form similar to that of estimators found in scikit-learn. If you have familiarity with the usage of estimators in scikit-learn, then working with estimators in alchemlyb should be somewhat straightforward.
alchemlyb provides implementations of many commonly-used estimators, which come in two varieties: TI-based and FEP-based.
estimators-ti estimators-fep