HANSEN: An Integrated Structural and Functional Proteome Resource for Structure-Guided Drug Discovery in Mycobacterium leprae

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Abstract

Leprosy remains a leading infectious cause of preventable disability, yet its causative agent, Mycobacterium leprae (M. leprae) , is structurally under-characterised. Only ten Protein Data Bank (PDB) entries represent seven of its 1,603 protein-coding genes. We present HANSEN, a proteome-wide structural and functional resource for M. leprae . Monomeric and oligomeric models were generated with AlphaFold 3, Boltz-1, Boltz-2 and Chai-1, and annotated with per-residue confidence, predicted aligned error and, for assemblies, interface confidence. Ligand-binding pockets were predicted with AF2BIND, P2Rank and fpocket, template-derived ligands were modelled within oligomeric complexes, residue-level B-cell epitope propensity was estimated with DiscoTope-3.0, and gene essentiality was transferred from Mycobacterium tuberculosis transposon-sequencing labels. These features are integrated in a relational database with interactive visualisation and combined into a calibrated Target Priority Score that ranks all 1,603 proteins into four tiers and recovers established antimycobacterial targets. HANSEN ( https://hansen-leprosy.medschl.cam.ac.uk/home ) provides a practical basis for target prioritisation and structure-guided drug discovery in leprosy.

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