TY - JOUR KW - Kinetics KW - Peptides KW - Protein Folding KW - Protein Structure, Secondary KW - Thermodynamics KW - Amino Acid Sequence KW - Molecular Sequence Data KW - Azo Compounds KW - Cross-Linking Reagents KW - Molecular Dynamics Simulation AU - B. Paoli AU - R. Pellarin AU - A. Caflisch AB -

The folding process of a 16-residue α-helical peptide with an azobenzene cross-linker (covalently bound to residues Cys3 and Cys14) is investigated by 50 molecular dynamics simulations of 4 μs each. The folding kinetics at 281 K show a stretched exponential behavior but become simpler and much faster when a distance restraint is used to emulate a nonbulky cross-linker. The free-energy basin of the helical state is divided into two subbasins by a barrier that separates helical conformations with opposite orientations of the Arg10 side chain with respect to the azobenzene cross-linker. In contrast, such barrier is not present in the helical basin of the peptide with the nonbulky cross-linker, which folds with speed similar to the unrestrained peptide. These results indicate that the cross-linker slows down folding because of steric hindrance rather than its restraining effect on the two ends of the helical segment.

BT - The Journal of Physical Chemistry B C1 - 0125 DA - 2010 Feb 11 DO - 10.1021/jp910216j IS - 5 J2 - J. Phys. Chem. B LA - eng M3 - Research Article N2 -

The folding process of a 16-residue α-helical peptide with an azobenzene cross-linker (covalently bound to residues Cys3 and Cys14) is investigated by 50 molecular dynamics simulations of 4 μs each. The folding kinetics at 281 K show a stretched exponential behavior but become simpler and much faster when a distance restraint is used to emulate a nonbulky cross-linker. The free-energy basin of the helical state is divided into two subbasins by a barrier that separates helical conformations with opposite orientations of the Arg10 side chain with respect to the azobenzene cross-linker. In contrast, such barrier is not present in the helical basin of the peptide with the nonbulky cross-linker, which folds with speed similar to the unrestrained peptide. These results indicate that the cross-linker slows down folding because of steric hindrance rather than its restraining effect on the two ends of the helical segment.

PY - 2010 SP - 2023 EP - 2027 T2 - The Journal of Physical Chemistry B TI - Slow folding of cross-linked alpha-helical peptides due to steric hindrance VL - 114 SN - 1520-5207 ER -