Following similar principles, designed novel AMPs based on Micrococcin 2, a thiopeptide with activity against Clostridium difficile . Micrococcin 2 binds tightly to a cleft between the 23S rRNA subunit and the L11 C-terminal domain (CTD), inhibiting the binding of elongation factor G (EF-G) . EF-G binding basically allows the ribosomes to continue "reading" the mRNA in order to translate it to the protein sequence. aimed to increase Micrococcin 2's solubility by adding highly polar groups to the scaffold, limiting its gastrointestinal absorption. The latter is fundamental to confine the drug in the intestinal lumen (where C. difficile resides and produces its toxins) while reducing the systemic exposure to the drug . These structural modifications were guided by docking generated poses and MM/GBSA calculations to assess the binding energy , underscoring the importance of structure-based design in optimizing compound properties.