Simulating biological charge transfer: Continuum dielectric theory or molecular dynamics?

Area of Science:

• Computational chemistry
• Biophysics
• Biochemistry

Background:

• Marcus's theory is crucial for understanding charge transfer.
• Bioenergetic problems often involve complex protein environments.
• Accurate thermodynamic parameters are essential for predicting reaction outcomes.

Purpose of the Study:

• To compare continuum dielectric theory and molecular dynamics for calculating charge transfer thermodynamic parameters.
• To investigate the synergistic relationship between these computational methods.
• To explore the influence of ions on charge transfer free energy landscapes.

Main Methods:

• Numerical solution of Poisson's equation for continuum dielectric theory.
• Thermodynamic integration using classical Newtonian molecular dynamics.
• Application to a nitrite reductase (NrfHA) protein heterodimer.

Main Results:

• Excellent agreement (1.7 kcal/mol RMSD) was found for driving forces between the two methods.
• A lower limit for reorganization energies was established.
• Molecular dynamics parameters improved dielectric theory computations, and dielectric theory rescaled reorganization energies.

Conclusions:

• Continuum dielectric theory and molecular dynamics are mutually supportive for studying charge transfer.
• These methods provide accurate insights into protein bioenergetics.
• Electrostatic calculations reveal the impact of Ca2+ ions on charge transfer free energy.