Mechanism of Action of Cyclophilin A Explored by Metadynamics Simulations
2009

How Cyclophilin A Works

publication Evidence: moderate

Author Information

Author(s): Leone Vanessa, Lattanzi Gianluca, Molteni Carla, Carloni Paolo

Primary Institution: International School for Advanced Studies (SISSA), Trieste, Italy

Hypothesis

The study investigates the mechanism of action of cyclophilin A in catalyzing prolyl isomerization in the HIV-1 capsid protein.

Conclusion

The enzyme cyclophilin A stabilizes a specific cis conformer of the HIV-1 capsid protein, facilitating its isomerization.

Supporting Evidence

  • Cyclophilin A significantly stabilizes the cis conformation of the HIV-1 capsid protein.
  • The study provides a novel four-step mechanism for the enzymatic process.
  • The findings are consistent with available molecular biology data.

Takeaway

Cyclophilin A helps a protein change shape, which is important for how the virus works. Understanding this can help in making new medicines.

Methodology

The study used metadynamics simulations to explore the isomerization of a peptide in water and in complex with cyclophilin A.

Limitations

The accuracy of the force field used in simulations may affect the results, particularly for transition states.

Digital Object Identifier (DOI)

10.1371/journal.pcbi.1000309

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