xProtCAS

xProtCAS identifies conserved accessible surfaces on protein structures to pinpoint interaction interfaces and infer functional and regulatory sites, including post-translational modification loci and regions affected by disease-associated mutations.

Key Features:

• Integration with AlphaFold2 Models: Uses structural models predicted by AlphaFold2 to analyze protein structures.
• Autonomous Structural Module Definition: Defines autonomous structural modules within predicted structures for localized analysis.
• Graph Representation of Modules: Transforms structural modules into graph representations that encode residue topology, accessibility, and conservation.
• Eigenvector Centrality-Based Approach: Applies an eigenvector centrality metric on module graphs to extract conserved surfaces and discriminate functional versus structural conservation constraints.

Scientific Applications:

• Protein Function Analysis: Identifies conserved accessible surfaces to support interpretation of protein function and regulation, including potential post-translational modification sites.
• Disease Mutation Impact Assessment: Highlights conserved surface regions that overlap disease-associated mutations to aid assessment of mutation impact.
• Proteome-wide Discovery: Enables application to the human proteome to reveal previously uncharacterized conserved surfaces, some containing clinically significant mutations.

Methodology:

Defines structural modules from AlphaFold2 models, converts modules into graphs encoding residue topology, accessibility, and conservation, and applies an eigenvector centrality-based method to identify conserved accessible surfaces and distinguish functional from structural conservation.