Nirmatrelvir is shown in Figure , A potential inhibitor of an enzyme, including that of the Mpro SARS-Cov-2 protease, has to have the physical capability of entering into its docked pose. The small molecule should be able to sample its available conforms without obstruction to enter and bind. Docking software does not model this process before binding, but only the binding based on molecular models and modeling and physical data. Two widely separated peaks, without any scores in a histogram between them, are disjoint and can be interpreted -large variation geometrically of the molecule, although allowed and keeping its stereoisomer, are in different conformational states which are not smoothly connected. Two widely separated peaks with populated states in energy between, i.e. smooth (probabilistic) density of states, can be connected by small changes in the molecule and conformations. This is important in determining if a computationally determined molecule is reasonable. As an extreme example, an isolated cavity deep within a protein without any physical pathway outlets is unreachable, but could score very high or elsewhere in a distribution of scores via docking calculations.