%0 Journal Article %J J Chem Phys %D 2005 %T Thermal unfolding of proteins. %A Cieplak, Marek %A Joanna I. Sulkowska %K Chemistry, Physical %K Computer Simulation %K Connectin %K Kinetics %K Models, Molecular %K Molecular Conformation %K Muscle Proteins %K Protein Conformation %K Protein Denaturation %K Protein Folding %K Protein Kinases %K Protein Structure, Secondary %K Proteins %K Temperature %K Time Factors %X Thermal unfolding of proteins is compared to folding and mechanical stretching in a simple topology-based dynamical model. We define the unfolding time and demonstrate its low-temperature divergence. Below a characteristic temperature, contacts break at separate time scales and unfolding proceeds approximately in a way reverse to folding. Features in these scenarios agree with experiments and atomic simulations on titin. %B J Chem Phys %V 123 %P 194908 %8 2005 Nov 15 %G eng %N 19 %R 10.1063/1.2121668 %0 Journal Article %J Acta Biochimica Polonica %D 2002 %T Computer simulations of protein folding with a small number of distance restraints %A Andrzej Sikorski %A Andrzej Koliński %A Jeffrey Skolnick %K Algorithms %K Amino Acids %K Amino Acids: chemistry %K Chemical %K Computer Simulation %K Hydrogen Bonding %K Models %K Molecular %K Monte Carlo Method %K Nerve Tissue Proteins %K Nerve Tissue Proteins: chemistry %K Plastocyanin %K Plastocyanin: chemistry %K Protein Conformation %K Protein Folding %K Protein Kinases %K Thermodynamics %X A high coordination lattice model was used to represent the protein chain. Lattice points correspond to amino-acid side groups. A complicated force field was designed in order to reproduce a protein-like behavior of the chain. Long-distance tertiary restraints were also introduced into the model. The Replica Exchange Monte Carlo method was applied to find the lowest energy states of the folded chain and to solve the problem of multiple minima. In this method, a set of replicas of the model chain was simulated independently in different temperatures with the exchanges of replicas allowed. The model chains, which consisted of up to 100 residues, were folded to structures whose root-mean-square deviation (RMSD) from their native state was between 2.5 and 5 A. Introduction of restrain based on the positions of the backbone hydrogen atoms led to an improvement in the number of successful simulation runs. A small improvement (about 0.5 A) was also achieved in the RMSD of the folds. The proposed method can be used for the refinement of structures determined experimentally from NMR data. %B Acta Biochimica Polonica %V 49 %P 683–692 %8 jan %G eng %U http://www.ncbi.nlm.nih.gov/pubmed/12422238 %R 024903683 %0 Journal Article %J Biophysical Journal %D 2002 %T Numerical study of the entropy loss of dimerization and the folding thermodynamics of the GCN4 leucine zipper %A Jorge Viñals %A Andrzej Koliński %A Jeffrey Skolnick %K Biophysical Phenomena %K Biophysics %K Databases as Topic %K Dimerization %K DNA-Binding Proteins %K DNA-Binding Proteins: chemistry %K Entropy %K Hot Temperature %K Leucine Zippers %K Models %K Monte Carlo Method %K Protein Folding %K Protein Kinases %K Protein Kinases: chemistry %K Saccharomyces cerevisiae Proteins %K Saccharomyces cerevisiae Proteins: chemistry %K Temperature %K Theoretical %K Thermodynamics %X A lattice-based model of a protein and the Monte Carlo simulation method are used to calculate the entropy loss of dimerization of the GCN4 leucine zipper. In the representation used, a protein is a sequence of interaction centers arranged on a cubic lattice, with effective interaction potentials that are both of physical and statistical nature. The Monte Carlo simulation method is then used to sample the partition functions of both the monomer and dimer forms as a function of temperature. A method is described to estimate the entropy loss upon dimerization, a quantity that enters the free energy difference between monomer and dimer, and the corresponding dimerization reaction constant. As expected, but contrary to previous numerical studies, we find that the entropy loss of dimerization is a strong function of energy (or temperature), except in the limit of large energies in which the motion of the two dimer chains becomes largely uncorrelated. At the monomer-dimer transition temperature we find that the entropy loss of dimerization is approximately five times smaller than the value that would result from ideal gas statistics, a result that is qualitatively consistent with a recent experimental determination of the entropy loss of dimerization of a synthetic peptide that also forms a two-stranded alpha-helical coiled coil. %B Biophysical Journal %V 83 %P 2801–2811 %8 nov %G eng %U http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1302364&tool=pmcentrez&rendertype=abstract %R 10.1016/S0006-3495(02)75289-2 %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