VIM-7 Metallo-β-lactamase
A carbapenem-hydrolysing metallo-β-lactamase from Pseudomonas aeruginosa — one of the most clinically urgent antibiotic resistance targets. Analysed end-to-end by the ResistAI pipeline.
Protein overview
Clinical significance
VIM-type MBLs confer resistance to virtually all β-lactam antibiotics including carbapenems — last-resort agents for Gram-negative infections. P. aeruginosa harbouring VIM genes causes life-threatening nosocomial infections with very limited therapeutic options. Inhibitor development targeting the active site zinc coordination is an active area of drug discovery.
Druggability analysis — fpocket
Note: Druggability scores are structural proxies computed by fpocket on AlphaFold-predicted structures (Le Guilloux et al. 2009). Thresholds: high ≥ 0.7, medium ≥ 0.4. Experimental validation is required to confirm binding site tractability.
Interpretation
fpocket identified 11 surface cavities in the AlphaFold-predicted VIM-7 structure. The top-ranked pocket (druggability score 0.747) corresponds to the active site zinc-binding cleft — a well-characterised pharmacological hotspot. A score above 0.7 indicates high predicted tractability for small-molecule inhibitor binding, consistent with published crystallographic and fragment screening data for VIM-type MBLs.
ESM-2 embedding similarity
480-dim cosine similarityESM-2 (esm2_t12_35M_UR50D) generated a 480-dimensional sequence embedding for VIM-7. ChromaDB cosine similarity search identified the five most structurally and evolutionarily related proteins in the 2,433-protein database — all confirmed metallo-β-lactamases, validating the biological coherence of the embedding space.
Pseudomonas aeruginosa
Escherichia coli
Klebsiella pneumoniae
Aeromonas hydrophila
Stenotrophomonas maltophilia
Key finding: All five nearest neighbours are experimentally characterised metallo-β-lactamases (VIM-1, VIM-2, NDM-1, CphA, L1), with cosine similarities of 0.97–0.99. This validates that ESM-2 embeddings capture functionally meaningful protein relationships without requiring structural alignment.
Relevant resistance literature
Discovery of Novel Inhibitor Scaffolds against the Metallo-β-lactamase VIM-2 by Surface Plasmon Resonance (SPR) Based Fragment Screening
J Med Chem · 2015
Structure-guided optimization of 1H-imidazole-2-carboxylic acid derivatives affording potent VIM-Type metallo-β-lactamase inhibitors
Eur J Med Chem · 2022
Fragment-based discovery of inhibitor scaffolds targeting the metallo-β-lactamases NDM-1 and VIM-2
Bioorg Med Chem Lett · 2016
Probing the Interaction of Aspergillomarasmine A with Metallo-β-lactamases NDM-1, VIM-2, and IMP-7
ACS Infect Dis · 2018
Pipeline summary
UniProt ID Q840P9 resolved — sequence and metadata fetched via UniProt REST API
3D structure retrieved from AlphaFold DB v4 (high-confidence predicted model)
fpocket detected 11 binding cavities — top pocket scored 0.747 (high druggability)
ESM-2 generated 480-dim sequence embedding — ChromaDB similarity search returned 5 MBL homologs (similarity 0.97–0.99)
RAG retrieved 4 directly relevant PubMed articles on VIM-type inhibitor discovery
Llama 3.3 70B synthesised PMID-cited research summary validating druggability assessment