SKEMPI

SKEMPI catalogs experimentally measured effects of mutations on protein–protein interactions to enable analysis of mutation impacts on binding affinity, kinetics, and thermodynamics in structure-resolved complexes.

Key Features:

• Manually curated mutation dataset: Contains 7,085 manually curated single and multiple mutations mapped to protein–protein complexes.
• Structure-resolved PPIs (PDB): Entries are linked to complex structures available in the Protein Data Bank (PDB).
• Binding free energy changes (ΔΔG): Reports experimental binding free energy changes for mutations to quantify effects on affinity.
• Kinetic rate constants: Provides changes in association and dissociation rate constants for 1,844 mutations.
• Thermodynamic parameters: Includes enthalpy and entropy changes for 443 mutations.
• Loss-of-binding annotations: Identifies 440 mutations that result in loss of detectable binding.

Scientific Applications:

• Mutation-impact analysis: Enables study of how sequence alterations affect binding affinity, kinetics, and thermodynamics.
• Protein engineering: Supports design and engineering of proteins with modified interaction properties.
• Signaling and complex regulation studies: Facilitates investigation of cellular signaling pathways and molecular complex regulation affected by interaction changes.
• Disease mechanism research: Aids analysis of how genetic mutations lead to loss or alteration of protein–protein interactions relevant to disease.

Methodology:

Manually curated experimental measurements of binding free energy, kinetic rate constants, and thermodynamic parameters are collected and mapped to PDB complex structures.