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Understanding hierarchical protein evolution from first principles.

N V Dokholyan1, E I Shakhnovich

  • 1Department of Chemistry, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA. dokh@wild.harvard.edu

Journal of Molecular Biology
|September 8, 2001
PubMed
Summary
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This study introduces a protein evolution model based on stability, explaining conserved amino acids and hierarchical protein families. It reveals distinct evolutionary timescales for sequence and structural similarity.

Area of Science:

  • Computational Biology
  • Protein Evolution
  • Biophysics

Background:

  • Proteins are organized hierarchically within fold families.
  • Understanding the evolutionary drivers of this organization is crucial.
  • Protein stability is a key factor in protein folding and function.

Purpose of the Study:

  • To propose a novel model explaining the hierarchical organization of proteins.
  • To investigate the role of native state stability in protein evolution.
  • To elucidate the evolutionary timescales governing protein family formation.

Main Methods:

  • Developed a dynamic model based on evolutionary selection by native state stability.
  • Analyzed the relaxation of the correlation function between mutations.

Related Experiment Videos

  • Derived a "profile" solution to predict conserved amino acid patterns.

    • Main Results:

    • The model successfully reproduces observed patterns of conserved amino acids across protein families.
    • Observed a separation of evolutionary timescales: short timescales form sequence and structure families, long timescales form structure families with low sequence similarity.
    • The model's dynamic nature provides insights into evolutionary time scales.

    Conclusions:

    • The proposed model offers a robust explanation for protein hierarchical organization and conserved amino acid patterns.
    • Native state stability is a significant evolutionary selection pressure.
    • The model elucidates distinct evolutionary trajectories at different time scales, impacting protein sequence and structural diversification.