Kinetics of peptide folding: computer simulations of SYPFDV and peptide variants in water.

摘要: The folding of Ser-Tyr-Pro-Phe-Asp-Val (SYPFDV), and sequence variants this peptide (SYPYD SYPFD) are studied computationally in an explicit water environment. An atomically detailed model the is embedded a sphere TIP3P molecules its optimal structure computed by simulated annealing. At distances from that beyond few solvation shells, continuum solvent employed. simulations performed using mean field approach enhances efficiency sampling conformations. computations predict small number conformations as plausible folded structures. All have type VI turn conformation for backbone, similar to found NMR. However, some structures differ experimentally proposed ones packing proline ring with aromatic residues. second most populated has, addition correctly same hydrophobic measured Our suggest kinetic mechanism consists three separate stages. time-scales associated these stages distinct depend differently on temperature. Electrostatic interactions play initial role guiding chain roughly correct end-to-end distance. time or later backbone torsions rearrange due local tendency form turn: step depends forces helped loose interactions. In final step, residues pack against each other. We also show existence off pathway intermediate, suggesting even "misfolded" can form. clearly parallel paths involved. findings process shares many features expected significantly larger protein molecules.