(16) Here, V 0 and V 1 are the potential energies at λ = 0 and 1, respectively and the notation ... λ signifies that the average should be taken over an MD simulation (NVT ensemble) of the Hamiltionian H(λ). In practice, the states at λ = 0 and 1 are typically taken as a harmonic system with free energy given by Eq. 12 and the fully anharmonic system as given by DFT, respectively. Simulations are then performed at different values of λ (by mixing harmonic and DFT forces) and the free energy is determined through numerical integration.