Evaluating potential Leclercia adecarboxylata transfer RNA sulfurtransferase inhibitors as therapeutic targets via molecular docking and dynamics simulations

Abstract Background Leclercia adecarboxylata is an emerging opportunistic pathogen that predominantly infects immunocompromised individuals and has recently exhibited increasing resistance to commonly used antibiotics. The limited availability of targeted therapies underscores the urgent need to identify novel drug candidates. In this study, an integrated in silico approach was used to identify potential phytochemical inhibitors of tRNA sulfurtransferase, a key protein involved in L. adecarboxylata pathogenesis and protein synthesis. Materials and methods A library of 28 plant-derived phytochemicals was virtually screened against the modeled and refined 3D structure of the target protein. Results Binding site prediction, docking studies, and pharmacophore analysis revealed that kuwanon D exhibited the strongest binding affinity (− 9.9 kcal/mol), along with favorable pharmacokinetic and safety profiles. ADMET evaluation and the Boiled-Egg model supported its drug-likeness, and good gastrointestinal absorption and toxicity screening indicated a non-toxic nature. Molecular dynamics simulations over 500 ns, followed by principal component analysis, free energy landscapes, and MM/GBSA, demonstrated the stability and favorable binding energetics of the kuwanon D-protein complex. Conclusion These results identify kuwanon D as a promising lead compound for developing targeted therapeutics against drug-resistant L. adecarboxylata , warranting in vitro and in vivo validation. Graphical Abstract Kuwanon D shows strong binding (− 9.9 kcal/mol) to Leclercia adecarboxylata tRNA sulfurtransferase, forming a stable, interaction-rich complex. In silico pharmacokinetics predict oral bioavailability, rule-of-five compliance, water solubility, and non-toxicity, highlighting Kuwanon D as a promising antibacterial lead.