In Silico Exploration of Cannabidiol Interactions with Outer Membrane Proteins in Salmonella Typhimurium LT2.

Cannabidiol (CBD), the non-psychoactive component of the hemp plant, has been investigated as a potential novel antimicrobial agent. This study was aimed at understanding the interactions between CBD and the outer membrane proteins (OMPs) of Salmonella Typhimurium LT2. Employing in silico techniques, we analyzed the binding affinities, interaction profiles, and drug-likeness of CBD with five independent OMP targets-OmpA, OmpC, OmpD, OmpF, and OmpX-together with a historical OmpD/nmpC receptor entry (legacy NmpC label). The molecular docking results showed varying predicted binding affinities across the evaluated OMP receptor entries, with OmpX exhibiting a docking score of -6.6 kcal/mol and the OmpD/nmpC legacy receptor entry, originally labeled "NmpC," exhibiting a score of -6.4 kcal/mol. The latter was retained for transparency but was not interpreted as an independent OMP target following annotation verification. The high sequence conservation observed among the analyzed OMPs further suggests that structurally similar regions may occur across multiple Salmonella strains. KEGG pathway mapping was used to provide functional context for OmpC and OmpF, including their association with two-component signaling and β-lactam-resistance pathways. These pathway analyses contextualize the biological roles of the porins but do not demonstrate that CBD directly alters the mapped pathways. Similarly, the docking analyses do not establish functional inhibition of these proteins or demonstrate effects on membrane integrity, bacterial survival, virulence, or antimicrobial susceptibility. Rather, the findings identify candidate CBD-OMP interactions and mechanistic hypotheses that warrant experimental validation. In conclusion, the in silico findings provide structural evidence of predicted interactions between CBD and selected OMPs of Salmonella Typhimurium LT2 and lay the foundation for further experimental studies to determine their biological significance.