Open AccessFree-Energy Landscapes of Proteins in the Presence and Absence of Force
Author(s) -
Zu Thur Yew,
Sergei V. Krivov,
Emanuele Paci
Publication year - 2008
Publication title -
the journal of physical chemistry. b
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 392
eISSN - 1520-6106
pISSN - 1520-5207
DOI - 10.1021/jp807316e
Subject(s) - non equilibrium thermodynamics , energy landscape , dictyostelium discoideum , physics , thermodynamic equilibrium , quasistatic process , statistical physics , protein folding , folding (dsp implementation) , classical mechanics , chemistry , thermodynamics , biochemistry , nuclear magnetic resonance , electrical engineering , gene , engineering
The equilibrium properties of the fourth immunoglobulin domain of filamin from Dictyostelium discoideum (ddFLN4) in the absence and presence of a small force (0-6 pN) pulling the termini apart is characterized through atomistic numerical simulation. The equilibrium free-energy landscape of ddFLN4 is found to change in a complex fashion that cannot be described in terms of one-dimensional projections as usually done in the interpretation of mechanical (un)folding experiments. Nonequilibrium unfolding simulations reveal that the major unfolding intermediate corresponds to a marginally populated state at equilibrium that only appears when a force larger than 4 pN is applied. Finally, we show that if the free-energy difference between states is taken to be linear in the applied force, the proportionality coefficient is not the difference in the end-to-end distance between pair of states as generally assumed even though the data can be reasonably fitted. The present results suggest that mechanical unfolding experiments may reveal states that are not accessible in the absence of force. Thus, special care should be taken when trying to interpret both equilibrium and nonequilibrium mechanical (un)folding experiments in light of the (un)folding properties in the absence of a force.