Here x is the configuration of the system, U is the potential energy, p the pressure and V the volume, plus any other terms relevant to the specific ensemble in which the simulation is run eg. N P T , grand, etc. As an example, consider the transformation of some ligand A to some ligand B. The value of λ ranges between 0 and 1, with a λ of 0 the system is in a state describing ligand A and with a λ of 1 the system is in a state describing ligand B. Typically λ will take multiple intermediate values between the end states 0 and 1; this range of λ values λ 0 , λ 0.1 , λ 0.2 ...λ 1 defines a set of alchemical states and simulations are performed in all these states. The choice of these states is not arbitrary and can affect both the accuracy and precision of the results.