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An analysis of conformational changes on protein-protein association: implications for predictive docking
1Biomolecular Modelling Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK.
Protein Engineering
|May 15, 1999
Summary
Protein complex formation involves significant conformational changes, particularly at the interface, supporting an induced fit model. However, simple lock-and-key models can approximate recognition due to limited changes in many systems.
Area of Science:
- Structural biology
- Biochemistry
- Computational biology
Background:
- Protein-protein interactions are fundamental to biological processes.
- Understanding conformational changes upon complex formation is crucial for drug design and systems biology.
- Existing models like lock-and-key and induced fit attempt to explain these interactions.
Purpose of the Study:
- To quantify and analyze conformational changes in protein complexes.
- To compare interface and non-interface residue movements.
- To assess the implications of these changes for predictive modeling.
Main Methods:
- Analysis of 39 pairs of complexed and unbound protein structures.
- Comparison with 12 pairs of independently solved identical protein structures.
- Evaluation of main chain and side chain movements.
Main Results:
- Over half of the studied protein complexes exhibit substantial conformational changes.
- Interface regions show significant movement directly related to complex formation.
- Exposed non-interface regions display movement due to inherent flexibility.
- Enzyme-inhibitor and antibody-antigen complexes show significant interface movements.
- Predictive docking remains successful despite large conformational changes.
Conclusions:
- The induced fit model generally describes protein complex formation.
- Limited conformational changes in many systems allow for a lock-and-key approximation.
- Structural flexibility and disorder contribute to movements in non-interface regions.