sentences:  The main issues are the interpretation of this "potential" as a true, physically valid potential of mean force, the nature of the reference state and its optimal formulation, and the validity of generalizations beyond pairwise distances.The first, qualitative justification of PMFs is due to Sippl, and
  based on an analogy with the statistical physics of liquids.For liquids,
  the potential of mean force is related to the radial distribution function formula_30, which is given by