Modeling of leucine zippers using molecular dynamics

GCN4-p1 is a peptide containing 33 amino acids which is the dimerization domain of the yeast transcriptional activator GCN4. Computer modeling and molecular dynamics were used to determine interactions important in parallel versus antiparallel alignment of two d-helical GCN4-p1 monomers. CHARMM and the Replica Path method were used to build dimeric models of GCN4-p1 with parallel and antiparallel alignments of the coiled coils. Energy parameters, such as solvent Accessible Surface Area, Hydrophobic Free Energy, and Solvation Free Energy were used to evaluate protein packing and stability. It is estimated that, in the absence of side chain charges, the modeled GCN4-p1 dimer with antiparallel alignment is between 2.5 and 3 kilocalories/mole more stable than the parallel GCN4-p1 crystal structure and approximately 4 kilocalories/mole more stable than the modeled parallel GCN4-p1 dimeric structure.