CASTp

CASTp identifies and quantifies concave surface regions (surface pockets and buried voids) on three-dimensional protein structures to characterize pocket geometry, lining atoms, and metric properties relevant to structure-function relationships and ligand design.

Key Features:

• Identification and Measurement: Detects pockets, cavities, and mouth openings and specifies lining atoms while calculating volume, area, and circumference using solvent accessible surface models (Richards' surface) and molecular surface models (Connolly's surface).
• Analytical Computation: Employs an analytically exact method grounded in computational geometry using alpha shape theory and discrete flow theory, including the duality between alpha complex and weighted Voronoi decomposition, to compute metric properties.
• Functional Annotation: Maps and reports annotated functional information from the Protein Data Bank (PDB), Swiss-Prot, and Online Mendelian Inheritance in Man (OMIM), including specific amino acid positions and variant single nucleotide polymorphisms (SNPs).

Scientific Applications:

• Ligand Design: Identifies and measures binding pockets and ancillary cavities to inform structure-based ligand design and pocket recruitment strategies.
• Protein Function Analysis: Relates surface topography and pocket-lining residues to physicochemical properties and potential functional sites in proteins.
• Structural Stability Studies: Characterizes internal cavities that may host structural water molecules or influence conformational stability and dynamics.
• Disease Research: Maps disease-related residues and variant SNPs to surface pockets and voids to assess potential impacts on protein function.

Methodology:

Computational geometry methods based on alpha shape theory and discrete flow theory using the duality between alpha complex and weighted Voronoi decomposition provide analytically exact metric computations, with solvent accessible (Richards' surface) and molecular (Connolly's surface) models for surface measures, and semi-global pair-wise sequence alignment to map functional annotations from databases onto structures.