MeLAD

MeLAD curates a database of structurally resolved metalloenzyme–ligand interactions to enable analysis of binding mechanisms, metal-binding pharmacophores (MBPs), and predictive association discovery for drug discovery.

Key Features:

• Dataset: MeLAD contains 6,086 structurally resolved interactions involving 1,416 distinct metalloenzymes and 3,564 ligands.
• Interaction categories: Interactions are classified as classical metal-binding (63.0%), non-classical metal-binding (2.3%), non-metal-binding (34.4%), and metal water-bridging (0.3%).
• Metal-binding pharmacophores (MBPs): Expanded associations represented by MBPs are linked to active site metal ions and coordination modes and include 263 monodentate, 191 bidentate, and 15 tridentate MBP chemotypes.
• Similarity-derived associations: Deductive associations derived from metalloenzyme structural similarity (MeSIM) and ligand chemical similarity (LigSIM) analyses number 3,726 and 52,740, respectively.
• Metalloenzyme profiling: Provides metalloenzyme profiling predictions for small molecules to evaluate potential interactions.

Scientific Applications:

• Drug discovery: Identification and prioritization of ligands that interact with metalloenzyme active sites for therapeutic development.
• Binding mechanism analysis: Elucidation of metal coordination modes and binding mechanisms in metalloenzymes based on structural interactions.
• MBP chemotype characterization: Comparative analysis of monodentate, bidentate, and tridentate MBP chemotypes and their metal ion associations.
• Predictive association inference: Inference of candidate metalloenzyme–ligand associations via MeSIM and LigSIM similarity analyses and small-molecule profiling.

Methodology:

Curated structurally resolved metalloenzyme–ligand interactions and generated deductive associations using metalloenzyme structural similarity (MeSIM) and ligand chemical similarity (LigSIM) analyses, with MBPs represented and linked to active site metal ions and coordination modes.