%0 Journal Article %J Biochemistry %D 1996 %T Method for predicting the state of association of discretized protein models. Application to leucine zippers. %A Michal Vieth %A Andrzej Koliński %A Jeffrey Skolnick %K Amino Acid Sequence %K Leucine Zippers %K Molecular Sequence Data %K Protein Folding %X A method that employs a transfer matrix treatment combined with Monte Carlo sampling has been used to calculate the configurational free energies of folded and unfolded states of lattice models of proteins. The method is successfully applied to study the monomer-dimer equilibria in various coiled coils. For the short coiled coils, GCN4 leucine zipper, and its fragments, Fos and Jun, very good agreement is found with experiment. Experimentally, some subdomains of the GCN4 leucine zipper form stable dimeric structures, suggesting the regions of differential stability in the parent structure. Our calculations suggest that the stabilities of the subdomains are in general different from the values expected simply from the stability of the corresponding fragment in the wild type molecule. Furthermore, parts of the fragments structurally rearrange in some regions with respect to their corresponding wild type positions. Our results suggest for an Asn in the dimerization interface at least a pair of hydrophobic interacting helical turns at each side is required to stabilize the stable coiled coil. Finally, the specificity of heterodimer formation in the Fos-Jun system comes from the relative instability of Fos homodimers, resulting from unfavorable intra- and interhelical interactions in the interfacial coiled coil region. %B Biochemistry %V 35 %P 955–967 %G eng %U http://www.ncbi.nlm.nih.gov/pubmed/8547278 %R 10.1021/bi9520702 %0 Journal Article %J Journal of Molecular Biology %D 1995 %T Prediction of quaternary structure of coiled coils. Application to mutants of the GCN4 leucine zipper %A Michal Vieth %A Andrzej Koliński %A Charles L. Brooks III %A Jeffrey Skolnick %K Computer Simulation %K DNA-Binding Proteins %K Fungal Proteins %K Fungal Proteins: chemistry %K Hydrogen Bonding %K Leucine Zippers %K Monte Carlo Method %K Mutation %K Protein Conformation %K Protein Folding %K Protein Kinases %K Protein Kinases: chemistry %K Saccharomyces cerevisiae Proteins %K Thermodynamics %X Using a simplified protein model, the equilibrium between different oligomeric species of the wild-type GCN4 leucine zipper and seven of its mutants have been predicted. Over the entire experimental concentration range, agreement with experiment is found in five cases, while in two cases agreement is found over a portion of the concentration range. These studies demonstrate a methodology for predicting coiled coil quaternary structure and allow for the dissection of the interactions responsible for the global fold. In agreement with the conclusion of Harbury et al., the results of the simulations indicate that the pattern of hydrophobic and hydrophilic residues alone is insufficient to define a protein's three-dimensional structure. In addition, these simulations indicate that the degree of chain association is determined by the balance between specific side-chain packing preferences and the entropy reduction associated with side-chain burial in higher-order multimers. %B Journal of Molecular Biology %V 251 %P 448–67 %8 aug %G eng %U http://www.ncbi.nlm.nih.gov/pubmed/7650742 %R 10.1006/jmbi.1995.0447