It has been previously reported that the retroinverso analog of S peptide cannot mimic the S peptide, whereas the retroinverso analog of foot-and-mouth disease virus antigen can mimic the foot-and-mouth disease virus antigen. The structures of S peptide, foot-and-mouth disease virus antigen, and their retroinverso analogs are known. Here, we have attempted to explain the structural basis of mimetics at the level of atomic interactions by elaborating upon the Guptasarma’s hypothesis. Using interaction energy analysis of S peptide and foot-and-mouth disease virus antigen, we propose that if the energy of the CO and NH backbone atoms’ non-covalent interactions with all other atoms is negligible as compared with the energy of other non-covalent interactions, then the retroinverso isomer can mimic the original peptide/protein. Previous work has established that the structure of the inverso analog of a protein will be the mirror image of the protein, and it will only recognize the respective mirror image substrate/binding partner. The retro peptide conformation that can be superimposed on all side chains in any conformation of the original peptide does not exist in the conformational space of the peptides.