De novo simulations of the folding thermodynamics of the GCN4 leucine zipper.
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.
Mohanty
D
D
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Kolinski
A
A
Skolnick
J
J
D003198:Computer Simulation; D004268:DNA-Binding Proteins; D019281:Dimerization; D005656:Fungal Proteins / Q000737:chemistry*; D016350:Leucine Zippers; D009010:Monte Carlo Method; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D011494:Protein Kinases / Q000737:chemistry*; D017433:Protein Structure, Secondary; D029701:Saccharomyces cerevisiae Proteins; D013696:Temperature; D013816:Thermodynamics
D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases