The statistics is briefly discussed and a protein-ligand interaction, conformational, and entropic, analysis is given for two molecules in particular from the method. The 2 molecules are: 1) Nirmatrelvir covalently and non-covalently (pre-covalent) bound to SARS-Cov-2 Mpro, and 2) BAM-15, a protonophore mitochondrial uncoupler with the enzyme CYP 3A4. The first is in a non-covalent and covalent ligand interaction analysis at the atomic level, and the second is in a small modification to obtain a less liver interacting, and potentially longer lasting in the body, variation. The free energy calculation was demonstrated for the first in both the inter-molecular interaction and the bound ligand entropy.