Switch from thermal to force-driven pathways of protein refolding

Abstract

The impact of the quenched force on protein folding pathways and free energy landscape was studied in detail. Using the coarse-grain Go model, we have obtained the low, middle, and high force regimes for protein refolding under the quenched force. The folding pathways in the low force regime coincide with the thermal ones. A clear switch from thermal folding pathways to force-driven pathways in the middle force regime was observed. The distance between the denatured state and transition state x in the temperature-driven regime is smaller than in the force-driven one. The distance x obtained in the middle force regime is consistent with the available experimental data suggesting that atomic force microscopy experiments deal with the force-regime which is just above the thermal one.

Refolding of Homopolymer Under Quenched Force

“…We have shown that, similar to the protein case [21], there exists the switch from the lowforce to the high-force regime where changes. The difference in folding pathways was demonstrated through different FELs for these regimes.…”

“…Using this CG model we have observed a switch from thermal to force-driven pathways of homopolymer refolding. Similar to the protein case [21] these two regimes are characterized by different values of measuring the distance from the transition state to the denaturate one. It would be interesting to test the prediction followed from our homopolymer unfolding simulation by experiment.…”

“…The distance between TS and DS of a N = 16 homopolymer is lower than that of proteins with more than 16 residues [21]. In order to make a more precise comparison we considered a β-hairpin which also has 16 beads.…”

“…4a). To study folding kinetics of this peptide we have used the Go model developed by Clementi and Onuchic [27] with the set of parameters given in our earlier work [21]. One can show that in the absence of external force the folding is fastest at .…”

“…Motivated by experimental works [14 -18], the refolding of proteins under quenched force has been considered by simulation [19,20]. In particular, recently we have disclosed [21] that the switch from the thermal to force-driven regime occurs at the critical force separating the folded state from the unfolded one. At low forces folding pathways coincide with those of folding in the absence of the external force.…”