Side-chain dynamics and protein folding.
The processes by which protein side chains reach equilibrium during a folding reaction are investigated using both lattice and all-atom simulations. We find that rates of side-chain relaxation exhibit a distribution over the protein structure, with the fastest relaxing side chains located in positions kinetically important for folding. Traversal of the major folding transition state corresponds to the freezing of a small number of side chains, belonging to the folding nucleus, whereas the rest of the protein proceeds toward equilibrium via backbone fluctuations around the native fold. The postnucleation processes by which side chains relax are characterized by very slow dynamics and many barrier crossings, and thus resemble the behavior of a glass.
Kussell
Edo
E
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Shimada
Jun
J
Shakhnovich
Eugene I
EI
D000596:Amino Acids / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry; D003198:Computer Simulation; D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics
D000596:Amino Acids; D001426:Bacterial Proteins; C034284:IgG Fc-binding protein, Streptococcus; D011506:Proteins