%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 International Journal of Quantum Chemistry %D 1999 %T De novo predictions of the quaternary structure of leucine zippers and other coiled coils %A Jeffrey Skolnick %A Andrzej Koliński %A Debasisa Mohanty %K coiled coil %K lattice protein models %K Leucine Zippers %K protein structure prediction %K quaternary structure prediction %X Coiled coils possess a quaternary structure comprised of the side-by-side arrangement of a-helices. Due their inherent structural simplicity, they are ideal model systems for both theoretical and experimental studies. Among the coiled coils are the leucine zippers, which play an important role in the activation of DNA transcription. In contrast to the large amount of available experimental data, an overview of which is presented, there are very few theoretical studies. To address this need, the status of existing theoretical approaches to predict coiled coil quaternary structure is described. Furthermore, to treat the conformational equilibria inherent in these systems, an extension of entropy sampling Monte Carlo simulations is developed that can treat multimers. Here, the approach is applied to GCN4 leucine zippers in the context of a reduced protein model. Not only is the native conformation successfully predicted, but the model also reproduces the experimentally observed helix content in the denatured state and the observed two-state thermodynamic behavior. Such two-state behavior arises from the dissociation of highly helical dimeric chains to form monomers of low, isolated chain helix content. %B International Journal of Quantum Chemistry %V 75 %P 165–176 %G eng %U http://cssb.biology.gatech.edu/skolnick/publications/pdffiles/183.pdf %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