From the internal binding energy and entropy, the Hemholtz free energy F=E-TS can be calculated and also broken into conformational modes using the distribution of states. In molecular simulations , pressure or volume is of interest because the box type and size can be fixed and subject to constant in either. In this case, Gibbs energy and enthalpy have to be addressed, and the statistical formulae apply there. 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 6(a); this shows up in the size of the entropic term, which is still much smaller but nonnegligible in the total free energy.