Fuzzle 2.0

Fuzzle 2.0 identifies and catalogs subdomain-sized evolutionary related protein fragments to enable analysis of their structural, functional, and ligand-binding roles across protein folds.

Key Features:

• Identification of Evolutionary Related Fragments: Contains over 1,000 subdomain-sized fragments shared across different protein folds that reflect assembly by duplication and recombination.
• Cross-fold Comparative Analysis: Analyzes fragments for shared features across different protein folds to reveal conserved structural and functional elements.
• Integration of Ligand Binding Data: Associates fragments with ligand binding information to identify conserved modes of ligand interaction and ligand-binding fragments.
• Resource for Protein Engineering: Provides fragment-level building blocks that support grafting of binding pockets and transfer of functional sites via fragment recombination.

Scientific Applications:

• Structural Biology: Analysis of conserved subdomain-sized fragments yields insights into protein structural organization and evolution.
• Evolutionary Biology: Shared fragments and conserved ligand-binding modes are used to trace evolutionary relationships and support hypotheses of common ancestry.
• Protein Engineering: Fragment repositories enable recombination and grafting strategies to design novel proteins and transfer functional sites.

Methodology:

Fuzzle 2.0 employs a pipeline developed to identify evolutionary related protein fragments, analyzes these fragments for shared features across different protein folds, and integrates ligand binding information.