A variety of options are available to incorporate entropic contributions to ∆G. The most common approach is normal mode analysis but it can require similar computational effort to the underlying simulations in order to obtain converged results . Consequently, here we explore the use of another, more computationally efficient, alternative approach proposed by Duan et al. . In their formulation the "variational entropy" can be derived from the fluctuations of the receptor-ligand interaction energy, E inter . This energy can be calculated using components of the MMPBSA calculation: