SWOTein

SWOTein predicts residue-level contributions to protein folding free energy from protein three-dimensional structures to identify stability strengths and weaknesses.

Key Features:

• Structure-Based Analysis: Uses protein three-dimensional structures to assess local residue contributions and interactions along the chain.
• Statistical Energy Functions: Employs three statistical energy functions—local interactions, hydrophobic forces, and tertiary interactions—to compute residue contributions.
• Complementary Insights: Compares different energy terms to provide complementary information on residue-level stability strengths and weaknesses.
• Validation and Application: Predictions have been validated against native hydrogen exchange data (e.g., apocytochrome b562) and applied to an amino acid-binding protein to identify a hinge involved in conformational change.
• Efficiency and Accuracy: Implements a fast computational approach suitable for large-scale analyses of folding and molecular recognition.

Scientific Applications:

• Protein Engineering: Guides engineering decisions by identifying residues to stabilize or destabilize to modulate folding and function.
• Conformational Change Mapping: Identifies critical regions, such as hinges, involved in conformational changes.
• Folding and Molecular Recognition Studies: Provides residue-level folding free energy maps to support studies of folding energetics and molecular recognition.

Methodology:

Calculates residue contributions to folding free energy from protein three-dimensional structures using three statistical energy functions (local interactions, hydrophobic forces, tertiary interactions) and categorizes residues as stability strengths or weaknesses.