A structure-based model fails to probe the mechanical unfolding pathways of the titin I27 domain

Abstract

We discuss the use of a structure based C$\alpha$-Go model and Langevin dynamics to study in detail the mechanical properties and unfolding pathway of the titin I27 domain. We show that a simple Go-model does detect correctly the origin of the mechanical stability of this domain. The unfolding free energy landscape parameters $x_u$ and $\Delta G^{‡}$, extracted from dependencies of unfolding forces on pulling speeds, are found to agree reasonably well with experiments. We predict that above $v=10^4$ nm/s the additional force-induced intermediate state is populated at an end-to-end extension of about $75\mathring{A}$. The force-induced switch in the unfolding pathway occurs at the critical pulling speed $v_{crit}\approx 10^6-10^7$ nm/s. We argue that this critical pulling speed is an upper limit of the interval where Bell's theory works. However, our results suggest that the Go-model fails to reproduce the experimentally observed mechanical unfolding pathway properly, yielding an incomplete picture of the free energy landscape. Surprisingly, the experimentally observed intermediate state with the A strand detached is not populated in Go-model simulations over a wide range of pulling speeds. The discrepancy between simulation and experiment is clearly seen from the early stage of the unfolding process which shows the limitation of the Go model in reproducing unfolding pathways and deciphering the complete picture of the free energy landscape.

31 pages, 9 figures, 1 table, supplementary material document

References in corpus (8)

• Refolding upon force quench and pathways of mechanical and thermal unfolding of ubiquitin
• Changing the mechanical unfolding pathway of FnIII10 by tuning the pulling strength
• New force replica exchange method and protein folding pathways probed by force-clamp technique
• Dependence of protein mechanical unfolding pathways on pulling speeds
• Folding of the Protein Domain hbSBD
• Protein mechanical unfolding: importance of non-native interactions
• A structure-based model fails to probe the mechanical unfolding pathways of the titin I27 domain
• New method for deciphering free energy landscape of three-state proteins

Cited by in corpus (4)

• A structure-based model fails to probe the mechanical unfolding pathways of the titin I27 domain
• Understanding the dependence on the pulling speed of the unfolding pathway of proteins
• Relevance of the speed and direction of pulling in simple modular proteins
• Modelling the unfolding pathway of biomolecules: theoretical approach and experimental prospect