wLake

wLake identifies clusters of conserved water molecules within superimposed three-dimensional (3D) structures of proteins and macromolecular complexes to delineate water-mediated intra- and intermolecular interactions.

Key Features:

• Conserved water detection: Identifies water molecules that occupy nearly identical positions across sets of superimposed 3D structures.
• Graph-based maximal-clique algorithm: Reduces conserved-water detection to finding maximal cliques in a graph representing spatial relationships among waters from different structures.
• Supports protein and DNA complexes: Analyzes waters immobilized on protein and DNA surfaces to predict functionally significant positions.
• Scalability and complexity: Employs an algorithm with exponential worst-case complexity but optimized to process dozens of superimposed structures efficiently.

Scientific Applications:

• Enzyme active sites: Predicts functionally significant water molecules in enzyme active sites, demonstrated on transketolases.
• Intermolecular interactions: Analyzes water-mediated contacts in protein–DNA complexes such as ETS–DNA assemblies.
• Intramolecular interactions: Examines water involvement in intramolecular processes, including thiol–disulfide interchange proteins.

Methodology:

Constructs a graph of spatial relationships among water molecules in superimposed 3D structures and identifies conserved sites by finding maximal cliques; algorithmic approach has exponential complexity.