Screening of promising molecules against potential drug targets in Yersinia pestis by integrative pan and subtractive genomics, docking and simulation approach

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.