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

Vedithi, S. C.; Rees, R.; Malhotra, S.; Munir, A.; Matusevicius, M.; Alsulami, A. F.; Beaudoin, C. A.; Sunkara, K. S.; Das, M.; Blundell, T. L.; Floto, R. A.

doi:10.64898/2026.08.03.741541

bioRxiv · 10.64898/2026.08.03.741541

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

Vedithi, S. C.·Rees, R.·Malhotra, S.·Munir, A.·Matusevicius, M.·Alsulami, A. F.·Beaudoin, C. A.·Sunkara, K. S.·Das, M.·Blundell, T. L.·Floto, R. A.

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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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Vedithi, S. C., Rees, R., Malhotra, S., Munir, A., Matusevicius, M., Alsulami, A. F., Beaudoin, C. A., Sunkara, K. S., Das, M., Blundell, T. L., Floto, R. A.. 2026-08-07. HANSEN: An Integrated Structural and Functional Proteome Resource for Structure-Guided Drug Discovery in Mycobacterium leprae. https://doi.org/10.64898/2026.08.03.741541

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