Two example calculations are given, non-covalently bound Nirmatrelvir and covalently bound. The zero energy state is referred to as free ligand. The entropic energy null contribution of ground state is made by assuming a unique ground bound state. The numerically calculated distribution is used, and no curve is used or required. An example calculation of E and S is given from the distribution in Figure The probabilities of the states less than about 58 are negligibly populated, being about 12/6.5=1.84 kcal, or one width of 1 kcal/𝑘 𝐵 𝑇 and this is seen in the calculated distribution and thermally weighted Boltzmann 𝑝(𝑍 𝑖 ) values . The mean of the distribution is score 49 and to get that from an expected energy requires T well beyond the boiling point of water, in the tens of thousands of Kelvins. Nirmatrelvir does have 9 rotatable bonds, is somewhat flexible even when bound, and these aspects show in the distributions of Figures ) and 8; this shows up in the size of the entropic term, which is still much smaller but non-negligible in the total free energy.