SMAP WS

SMAP WS performs proteome-wide 3D ligand-binding site comparison and similarity searching to analyze protein structure, function, and evolution.

Key Features:

• Proteome-scale 3D binding-site comparison: Enables large-scale comparison and similarity searching of 3D ligand-binding sites across structural proteomes.
• Geometric Potential (shape descriptor): Characterizes local and global topological properties of protein structures and predicts ligand-binding pockets.
• SOIPPA (Sequence Order Independent Profile-Profile Alignment): Detects and aligns similar binding pockets independent of sequence order to reveal functional and evolutionary relationships across diverse folds.
• Statistical significance estimation (Extreme Value Distribution): Uses an extreme value distribution model to estimate significance of binding-site matches for local sequence order-independent similarity searches.

Scientific Applications:

• Protein structure-function-evolution analysis: Facilitates proteome-scale studies of protein structure, function, and evolutionary relationships via binding-site comparisons.
• Genome-based drug discovery and validation: Supports genome-based drug discovery and validation by identifying binding-site similarities and potential off-targets.
• Prediction of drug side effects: Applied to detect unintended binding-site similarities that can explain or predict drug side effects.
• Drug repurposing: Enables identification of existing drugs with potential new therapeutic indications through binding-site similarity.

Methodology:

SMAP WS applies a geometric potential shape descriptor, sequence order-independent profile-profile alignment (SOIPPA), large-scale 3D ligand-binding site comparison, and extreme value distribution modeling to perform local sequence order-independent similarity searching across structural proteomes.