De Novo simulations of the folding thermodynamics of the GCN4 leucine zipper

Entropy Sampling Monte Carlo (ESMC) simulations were carried out to study t he thermodynamics of the folding transition in the GCN4 leucine zipper (GCN 4-lz) in the context of a reduced model. Using the calculated partition fun ctions for the monomer and dimer, and taking into account the equilibrium b etween the monomer and dimer, the average helix content of the GCN4-lz was computed over a range of temperatures and chain concentrations. The predict ed helix contents for the native and denatured states of GCN4-lz agree with the experimental values. Similar to experimental results, our helix conten t versus temperature curves show a small linear decline in helix content wi th an increase in temperature in the native region. This is followed by a s harp transition to the denatured state. van't Hoff analysis of the helix co ntent versus temperature curves indicates that the folding transition can b e described using a two-state model. This indicates that knowledge-based po tentials can be used to describe the properties of the folded and unfolded states of proteins.