Reliable protein folding on complex energy landscapes: the free energy reaction path.
A theoretical framework is developed to study the dynamics of protein folding. The key insight is that the search for the native protein conformation is influenced by the rate r at which external parameters, such as temperature, chemical denaturant, or pH, are adjusted to induce folding. A theory based on this insight predicts that 1), proteins with complex energy landscapes can fold reliably to their native state; 2), reliable folding can occur as an equilibrium or out-of-equilibrium process; and 3), reliable folding only occurs when the rate r is below a limiting value, which can be calculated from measurements of the free energy. We test these predictions against numerical simulations of model proteins with a single energy scale.
Lois
Gregg
G
Department of Physics, Yale University, New Haven, Connecticut, USA. gregg.lois@yale.edu
Blawzdziewicz
Jerzy
J
O'Hern
Corey S
CS
D007700:Kinetics; D008958:Models, Molecular; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D013696:Temperature; D013816:Thermodynamics