VASP

VASP performs comparative volumetric analysis of binding sites in aligned protein structures to identify structural variations that influence ligand binding specificity across evolutionarily related proteins.

Key Features:

• Volumetric Analysis: Represents protein overall shape and surface features such as cavities, clefts, and tunnels using solid volumetric representations for detailed binding-site comparison.
• Constructive Solid Geometry Techniques: Applies constructive solid geometry operations to three-dimensionally superposed volumes to isolate conserved and variable regions between structures.
• Isolation of Structural Variations: Pinpoints individual amino acids and cavity subregions that create structural distinctions between ligand-binding sites.

Scientific Applications:

• START domains: Analyzes ligand binding-site variations in steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domains to relate amino acid and cavity subregion differences to binding specificity.
• Serine proteases: Compares binding-site volumetric differences among serine proteases to identify structural determinants of divergent ligand specificity.

Methodology:

Aligns protein structures, converts them to solid volumetric representations, superposes volumes, and uses constructive solid geometry operations to identify conserved and variable regions and map these to specific amino acids and cavity subregions.