Abstract
This study aims to identify novel drug targets in Yersinia pestis, the bacterium responsible for plague, using an integrative approach combining pan-genomic and subtractive genomics methods. The primary objective was to locate targets that do not share homology with human proteins, gut microbiota, or known anti-targets but are crucial for the pathogen's survival. These targets should also exhibit high levels of protein interaction, antibiotic resistance, and conservation across various pathogens. We identified two promising targets: the aminotransferase class I/class II domain-containing protein and 3-oxoacyl-[acyl-carrier-protein] synthase 2. These proteins were modeled using AlphaFold2, validated through several structural analyses, and subjected to molecular docking and ADMET analysis. Molecular dynamics simulations confirmed the stability of the drug-target complexes, indicating their potential as targets for new therapies against Y. pestis.