Exploratory Computational Assessment of Lactiplantibacillus plantarum K25-Derived Fatty Acid Metabolites Against Leishmania donovani Centrin.

Probiotic derived metabolites have emerged as promising bio-active compounds with diverse antimicrobial and therapeutic applications. In the present study, an integrative metabolomic and computational approach was employed to investigate fatty acid metabolites produced by Lactiplantibacillus plantarum K25 and evaluate their potential activity against virulence associated targets to Leishmania donovani, the causative agent of visceral leishmaniasis (kala-azar). L. plantarum K25 exhibited robust growth across linoleic acid concentrations ranging from 1 to 10% (w/v), with maximum metabolite production during 24-36 h. The previously reported GC-MS dataset contained nine metabolites, including linoelaidic acid (8.08-9.73 mg/L), 9,12-octadecadienoic acid (Z, Z) (maximum 17.24 mg/L), and linolenic acid (0.02-0.03 mg/L). Among four virulence proteins retrieved, centrin (LDBPK_070790) showed antigenicity (0.5822) and was selected for downstream analysis. Molecular docking identified linoelaidic acid as the highest-ranked compound, with a predicted AutoDock Vina score of - 8.2 kcal/mol, although its binding specificity remains unverified. Molecular dynamics simulations were used to examine the conformational behavior of the predicted protein-ligand complex; however, these findings do not independently establish binding specificity or biological activity. Pharmacokinetic analysis showed high gastrointestinal absorption with bio-availability score of 0.85 and LogP of 5.45, while toxicity profiling indicated no major organ toxicity or mutagenicity. Overall, the predicted interaction of linoelaidic acid with centrin was favorable, and the binding was stable after molecular dynamics simulation for 210 ps, the predicted ADMET properties were favorable, and the predicted toxicity was low. The results obtained suggest that linoelaidic acid is a computational candidate which can be targeted in further experimental studies to investigate the activity against Leishmania donovani. This study highlights L. plantarum derived fatty acids as promising antileishmanial leads and provides a foundation for future experimental validation and drug development against visceral leishmaniasis.