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Kinetic versus energetic discrimination in biological copying
Pablo Sartori1, Simone Pigolotti
1Max Planck Institute for the Physics of Complex Systems, Noethnitzer Strasse 38, 01187 Dresden, Germany.
Physical Review Letters
|May 21, 2013
Summary
This study reveals that kinetic and energetic discrimination mechanisms in stochastic copying are alternative, not complementary, in single-step reactions. Analyzing DNA polymerases suggests distinct operational regimes for T7 and Polγ.
Area of Science:
- Biophysics
- Biochemistry
- Molecular Biology
Background:
- Stochastic copying processes are fundamental in biological systems.
- Discrimination between correct and incorrect matches is crucial for fidelity.
- Mechanisms include kinetic barriers and binding energies.
Purpose of the Study:
- To investigate stochastic copying schemes with kinetic or energetic discrimination.
- To determine if these mechanisms can be combined to improve accuracy.
- To analyze DNA polymerase kinetics in relation to these models.
Main Methods:
- Theoretical analysis of single-step reaction schemes.
- Thermodynamic and kinetic modeling of copying fidelity.
- Analysis of experimental kinetic rates for T7 and Polγ DNA polymerases.
Main Results:
- Kinetic and energetic discrimination are mutually exclusive in single-step reactions.
- Kinetic discrimination leads to high velocity but also high dissipation.
- Energetic discrimination achieves low error in a low-dissipation regime.
Conclusions:
- T7 and Polγ DNA polymerases likely operate in distinct kinetic and energetic regimes.
- Combining kinetic and energetic discrimination is possible in multi-step proofreading pathways.
- Understanding these mechanisms is key for designing accurate biological copying systems.
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