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CO migration pathways in cytochrome P450cam studied by molecular dynamics simulations
Liliane Mouawad1, Catherine Tetreau, Safwat Abdel-Azeim
1Inserm U759, Institut Curie-Recherche, Bâtiment 112, Université Paris-Sud, 91405 Orsay cedex, France. liliane.mouawad@curie.u-psud.fr
Protein Science : a Publication of the Protein Society
|April 3, 2007
Summary
Molecular dynamics simulations reveal seven hydrophobic CO docking sites within cytochrome P450(cam), explaining complex CO rebinding kinetics and protein dynamics.
Area of Science:
- Biochemistry
- Computational Biology
- Structural Biology
Background:
- Cytochrome P450(cam) exhibits complex CO rebinding kinetics.
- Previous studies suggest intricate internal protein dynamics after ligand dissociation.
Purpose of the Study:
- Explore carbon monoxide (CO) migration pathways in P450(cam).
- Identify internal cavities and CO docking sites.
- Correlate simulation findings with experimental rebinding kinetics.
Main Methods:
- Molecular dynamics simulations of the P450(cam)(cam)(CO) ternary complex.
- Simulations conducted at 200, 300, and 320 K in water and vacuum.
- Analysis of CO migration, internal cavities, and docking sites.
Main Results:
- Identified seven predominantly hydrophobic CO docking sites within the protein.
- Discovered eight persistent internal cavities, four correlating with docking sites.
- Observed water molecules preferentially occupying polar pockets, avoiding CO docking areas.
- Defined CO migration pathways consistent with experimental data.
Conclusions:
- Molecular dynamics simulations provide insights into CO rebinding mechanisms in P450(cam).
- The identified docking sites and pathways explain the complex kinetics observed experimentally.
- Protein internal dynamics and cavity structure play crucial roles in ligand interaction.
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