A Lattice Model Study of Native Contact Restraints in Protein Folding

摘要

To explore protein folding mechanism, we simulated a folding pathway in a simplified 3】3】3 cubic lattice. In the lattice folding Monte Carlo simulations, each of the 28 possible native packing pairs that exist in the native conformation was used as a conformational restraint. The native packing restraints in the lattice model could be considered as a disulfide linkage restraint in a real protein. The results suggest that proteins denatured with a small disulfide loop can, but not always, fold faster than proteins without any disulfide linkage and than proteins with a larger disulfide loop. The results also suggest that there is a rough correlation between loop size of the native packing restraint and folding time. That is, the order of native residue-residue packing interaction in protein folding is likely dependent on the residue-residue distance in primary sequence. The strength of monomer-monomer pairwise interaction is not important in the determination of the packing order in lattice folding. From the folding simulations of five strong folding lattice sequences, it was also found that the context encoded in the primary sequence, which we do not yet clearly understand, plays more crucial role in the determination of detailed folding kinetics. Our restrained lattice model approach would provide a useful strategy to the future protein folding experiments by suggesting a protein engineering for the fast or slow folding research.