Kinetic model for reversible radical transfer in ribonucleotide reductase

Area of Science:

• Biochemistry
• Molecular Biology
• Biophysics

Background:

• Ribonucleotide reductase (RNR) is crucial for DNA synthesis, replication, and repair.
• RNR function involves long-range radical translocation across protein subunits and an aqueous interface.
• Understanding this radical transfer is key to elucidating RNR's catalytic mechanism.

Purpose of the Study:

• To develop a kinetic model for reversible radical transfer in *Escherichia coli* RNR.
• To investigate radical transport dynamics through protein residues.
• To identify key rate constants influencing radical translocation efficiency.

Main Methods:

• Development of a kinetic model incorporating radical injection, transfer, and conformational changes.
• Utilizing experimental data from photoRNR systems for model parameterization.
• Employing quantum mechanical/molecular mechanical simulations for free-energy calculations.

Main Results:

• The kinetic model accurately describes radical injection and translocation dynamics.
• Rate constants for interfacial radical transfer were determined by fitting to experimental decay times.
• The model identifies specific residues and rate constants critical for efficient radical transport.

Conclusions:

• The developed kinetic model provides insights into the temporal evolution of radical transport in RNR.
• Key rate-limiting steps and tunable parameters for radical translocation were identified.
• Findings support biochemical understanding and protein engineering for potential pharmacological applications.