TY - JOUR
T1 - Reliable protein folding on complex energy landscapes
T2 - The free energy reaction path
AU - Lois, Gregg
AU - Blawzdziewicz, Jerzy
AU - O'Hern, Corey S.
N1 - Funding Information:
Financial support from National Science Foundation grants No. CBET-0348175 (to G.L. and J.B.) and DMR-0448838 (to G.L. and C.S.O.), and Yale's Institute for Nanoscience and Quantum Engineering (G.L.), is gratefully acknowledged. We also thank Yale's High Performance Computing Center for computing time.
PY - 2008/9/15
Y1 - 2008/9/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=55549115056&partnerID=8YFLogxK
U2 - 10.1529/biophysj.108.133132
DO - 10.1529/biophysj.108.133132
M3 - Article
C2 - 18515400
AN - SCOPUS:55549115056
SN - 0006-3495
VL - 95
SP - 2692
EP - 2701
JO - Biophysical Journal
JF - Biophysical Journal
IS - 6
ER -