Ras Conformational Switching: Simulating Nucleotide-Dependent Conformational Transitions with Accelerated Molecular Dynamics
2009

Ras Conformational Switching: Simulating Nucleotide-Dependent Conformational Transitions

publication Evidence: high

Author Information

Author(s): Grant Barry J., Gorfe Alemayehu A., McCammon J. Andrew

Primary Institution: University of California San Diego

Hypothesis

How does Ras change its structure during its enzymatic cycle and how do mutations affect this process?

Conclusion

The study reveals that nucleotide-dependent conformational transitions in Ras are critical for its signaling function and can be characterized using advanced simulation techniques.

Supporting Evidence

  • Ras proteins are critical for cell signaling and mutations can lead to cancer.
  • Advanced simulations revealed new insights into the conformational changes of Ras.
  • Identified intermediate structures provide a better understanding of Ras function.

Takeaway

Ras proteins switch between different shapes to help control cell growth, and this study shows how those shape changes happen using computer simulations.

Methodology

The study used accelerated molecular dynamics (aMD) simulations to characterize nucleotide-dependent conformational transitions in Ras.

Limitations

The study primarily focuses on wild-type Ras and may not fully capture the dynamics of all Ras variants.

Digital Object Identifier (DOI)

10.1371/journal.pcbi.1000325

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