Modeling electron transfer thermodynamics in protein complexes: interaction between two cytochromes c(3)

Area of Science:

• Biochemistry
• Molecular Biophysics
• Computational Biology

Background:

• Cytochromes c(3) are essential redox proteins involved in electron transfer pathways.
• Understanding protein-protein interactions is crucial for elucidating biological electron transport mechanisms.

Purpose of the Study:

• To analyze redox protein complexes formed between type I and type II tetraheme cytochromes c(3) from Desulfovibrio vulgaris Hildenborough.
• To investigate the stability and thermodynamic properties of these complexes using theoretical methodologies.

Main Methods:

• Rigid-body docking techniques were employed to generate various protein complexes.
• Molecular dynamics simulations with explicit solvent were used to relax the lowest energy complexes.
• Binding free energy calculations utilized molecular mechanics, Poisson-Boltzmann, and surface accessibility methods.

Main Results:

• Two stable complexes were identified, with complex 2 (heme IV of type I interacting with heme I of type II) being more stable than complex 1.
• Complex formation induced significant changes in the reduction potentials of both cytochromes c(3), particularly heme IV of type I.
• These changes inverted the global titration curves, facilitating directional electron transfer from type I to type II cytochrome c(3).

Conclusions:

• The formation of stable redox complexes between tetraheme cytochromes c(3) can thermodynamically drive directional electron transfer.
• These findings suggest a natural design principle for efficient biological redox chains.
• The study provides insights into the functional consequences of protein-protein interactions in electron transport systems.