Folding of a small helical protein using hydrogen bonds and hydrophobicity forces.
A reduced protein model with five to six atoms per amino acid and five amino acid types is developed and tested on a three-helix-bundle protein, a 46-amino acid fragment from staphylococcal protein A. The model does not rely on the widely used Go approximation, which ignores non-native interactions. We find that the collapse transition is considerably more abrupt for the protein A sequence than for random sequences with the same composition. The chain collapse is found to be at least as fast as helix formation. Energy minimization restricted to the thermodynamically favored topology gives a structure that has a root-mean-square deviation of 1.8 A from the native structure. The sequence-dependent part of our potential is pairwise additive. Our calculations suggest that fine-tuning this potential by parameter optimization is of limited use.
Favrin
Giorgio
G
Department of Theoretical Physics, Complex Systems Division, Lund University, Lund, Sweden.
Irbäck
Anders
A
Wallin
Stefan
S
D000595:Amino Acid Sequence; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009010:Monte Carlo Method; D010446:Peptide Fragments / Q000737:chemistry; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D013205:Staphylococcal Protein A / Q000737:chemistry; D013816:Thermodynamics
D010446:Peptide Fragments; D011506:Proteins; D013205:Staphylococcal Protein A