Stabilization of native and non-native structures by salt bridges in a lattice model of the GCN4 leucine dimer

J Phys Chem B. 2010 Jan 21;114(2):796-803. doi: 10.1021/jp909872a.


We use computer simulations to investigate the influence of salt bridges on the dimerization of the GCN4 leucine zipper. Use of a lattice model allows the dimerization process to be followed for time scales long enough to investigate large-scale structural changes traversing large distances in configuration space. We calculated the rate, efficiency, and stability of dimerization and free-energy landscapes. We varied the strength of the ionic interactions and find that there is an optimal, intermediate salt bridge strength at which the dimerization process proceeds at the maximum rate. Though especially strong salt bridge strength beneficially stabilizes native dimers if they form, it can also stabilize non-native configurations that can hinder the dimerization process. We give examples of stable, non-native structures that might arise. These structures may be relevant to interesting recent experiments that have provided evidence of unusual forms of the leucine zipper GCN4-p1 called the LZ(GCN4) x-forms, which dominate the population in certain biochemical conditions.

MeSH terms

  • Basic-Leucine Zipper Transcription Factors / chemistry*
  • Computer Simulation
  • Dimerization
  • Leucine / chemistry*
  • Leucine Zippers*
  • Models, Molecular
  • Protein Conformation
  • Protein Stability
  • Saccharomyces cerevisiae / chemistry*
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Salts / chemistry*


  • Basic-Leucine Zipper Transcription Factors
  • GCN4 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Salts
  • Leucine