Here λ (0 £ λ £ 1) is an alchemical coupling parameter such that λ=0 and λ=1 correspond to the initial and final thermodynamic states, and 𝜕𝑉(𝜆) 𝜕𝜆 ⁄ is the partial derivative of the hybrid potential energy V(λ) at an intermediate state l. 〈⋯ 〉 ; denotes an ensemble average over configurations representative of the state l.