%0 Journal Article %J Proteins %D 1999 %T Correlation between knowledge-based and detailed atomic potentials: application to the unfolding of the GCN4 leucine zipper %A Debasisa Mohanty %A Brian N. Dominy %A Andrzej Koliński %A Charles L. Brooks III %A Jeffrey Skolnick %K DNA-Binding Proteins %K Fungal Proteins %K Fungal Proteins: chemistry %K Leucine Zippers %K Protein Denaturation %K Protein Kinases %K Protein Kinases: chemistry %K Saccharomyces cerevisiae Proteins %K Thermodynamics %X The relationship between the unfolding pseudo free energies of reduced and detailed atomic models of the GCN4 leucine zipper is examined. Starting from the native crystal structure, a large number of conformations ranging from folded to unfolded were generated by all-atom molecular dynamics unfolding simulations in an aqueous environment at elevated temperatures. For the detailed atomic model, the pseudo free energies are obtained by combining the CHARMM all-atom potential with a solvation component from the generalized Born, surface accessibility, GB/SA, model. Reduced model energies were evaluated using a knowledge-based potential. Both energies are highly correlated. In addition, both show a good correlation with the root mean square deviation, RMSD, of the backbone from native. These results suggest that knowledge-based potentials are capable of describing at least some of the properties of the folded as well as the unfolded states of proteins, even though they are derived from a database of native protein structures. Since only conformations generated from an unfolding simulation are used, we cannot assess whether these potentials can discriminate the native conformation from the manifold of alternative, low-energy misfolded states. Nevertheless, these results also have significant implications for the development of a methodology for multiscale modeling of proteins that combines reduced and detailed atomic models. %B Proteins %V 35 %P 447–452 %G eng %U http://www.ncbi.nlm.nih.gov/pubmed/10382672 %0 Journal Article %J Biophysical Journal %D 1999 %T De novo simulations of the folding thermodynamics of the GCN4 leucine zipper %A Debasisa Mohanty %A Andrzej Koliński %A Jeffrey Skolnick %K Computer Simulation %K Dimerization %K DNA-Binding Proteins %K Fungal Proteins %K Fungal Proteins: chemistry %K Leucine Zippers %K Monte Carlo Method %K Protein Conformation %K Protein Denaturation %K Protein Folding %K Protein Kinases %K Protein Kinases: chemistry %K Protein Structure %K Saccharomyces cerevisiae Proteins %K Secondary %K Temperature %K Thermodynamics %X Entropy Sampling Monte Carlo (ESMC) simulations were carried out to study the thermodynamics of the folding transition in the GCN4 leucine zipper (GCN4-lz) in the context of a reduced model. Using the calculated partition functions for the monomer and dimer, and taking into account the equilibrium between the monomer and dimer, the average helix content of the GCN4-lz was computed over a range of temperatures and chain concentrations. The predicted helix contents for the native and denatured states of GCN4-lz agree with the experimental values. Similar to experimental results, our helix content versus temperature curves show a small linear decline in helix content with an increase in temperature in the native region. This is followed by a sharp transition to the denatured state. van't Hoff analysis of the helix content versus temperature curves indicates that the folding transition can be described using a two-state model. This indicates that knowledge-based potentials can be used to describe the properties of the folded and unfolded states of proteins. %B Biophysical Journal %V 77 %P 54–69 %8 jul %@ 6197848821 %G eng %U http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1300312&tool=pmcentrez&rendertype=abstract %R 10.1016/S0006-3495(99)76872-4 %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