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Related Experiment Videos

Evidence for strained interactions between side-chains and the polypeptide backbone

W E Stites1, A K Meeker, D Shortle

  • 1Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2185.

Journal of Molecular Biology
|January 7, 1994
PubMed
Summary
This summary is machine-generated.

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Unusual protein backbone structures create strain energy, reducing stability. This study quantifies this strain energy in staphylococcal nuclease, finding it can lower protein stability by up to 4 kcal/mol per residue.

Area of Science:

  • Protein structure and stability
  • Biophysics
  • Structural biology

Background:

  • Proteins contain residues with unusual backbone conformations (phi,psi angles).
  • These conformations can lead to unfavorable steric interactions and local strain energy.
  • Staphylococcal nuclease has 18 out of 133 residues in such unusual conformations.

Purpose of the Study:

  • To quantify the strain energy associated with unfavorable backbone conformations in proteins.
  • To determine the impact of these local interactions on protein stability.
  • To investigate the potential for relieving strain energy through specific mutations.

Main Methods:

  • Mutational analysis by replacing wild-type residues with glycine to access a wider range of phi,psi angles.

Related Experiment Videos

  • Comparing glycine mutants to alanine mutants to isolate the effect of backbone conformation.
  • Comparing free energy differences (delta delta GG-->A) to unstrained positions.
  • Introducing steric clashes by substituting alanine at specific glycine positions.

    • Main Results:

    • Residues with backbone angles outside preferred alpha-helical and beta-sheet regions contribute to local strain energy.
    • This strain energy lowers native state stability by 1-2 kcal/mol, and up to 3-4 kcal/mol in some cases.
    • An estimated 20 kcal/mol of strain energy exists in a 100-residue protein, potentially releasable by mutations.

    Conclusions:

    • Unfavorable backbone conformations represent a significant source of strain energy in proteins.
    • This strain energy can be quantified and potentially reduced through targeted mutagenesis.
    • Understanding and relieving protein strain energy may have implications for protein design and engineering.