Changing the mechanical unfolding pathway of FnIII10 by tuning the pulling strength

Abstract

We investigate the mechanical unfolding of the tenth type III domain from fibronectin, FnIII10, both at constant force and at constant pulling velocity, by all-atom Monte Carlo simulations. We observe both apparent two-state unfolding and several unfolding pathways involving one of three major, mutually exclusive intermediate states. All the three major intermediates lack two of seven native beta-strands, and share a quite similar extension. The unfolding behavior is found to depend strongly on the pulling conditions. In particular, we observe large variations in the relative frequencies of occurrence for the intermediates. At low constant force or low constant velocity, all the three major intermediates occur with a significant frequency. At high constant force or high constant velocity, one of them, with the N- and C-terminal beta-strands detached, dominates over the other two. Using the extended Jarzynski equality, we also estimate the equilibrium free-energy landscape, calculated as a function of chain extension. The application of a constant pulling force leads to a free-energy profile with three major local minima. Two of these correspond to the native and fully unfolded states, respectively, whereas the third one can be associated with the major unfolding intermediates.

15 pages, 9 figures

References in corpus (15)

• A nonequilibrium equality for free energy differences
• The Entropy Production Fluctuation Theorem and the Nonequilibrium Work Relation for Free Energy Differences
• Experimental Free Energy Surface Reconstruction From Single-Molecule Force Spectroscopy Using Jarzynski's Equality
• Forced-unfolding and force-quench refolding of RNA hairpins
• Monte Carlo Update for Chain Molecules: Biased Gaussian Steps in Torsional Space
• Folding thermodynamics of peptides
• An Ising-Like model for protein mechanical unfolding
• Thermodynamics of alpha- and beta-structure formation in proteins
• Refolding upon force quench and pathways of mechanical and thermal unfolding of ubiquitin
• Mechanical unfolding and refolding pathways of ubiquitin
• Reconstructing the free energy landscape of a polyprotein by single-molecule experiments
• Reconstructing the free energy landscape of a mechanically unfolded model protein
• Protein mechanical unfolding: a model with binary variables
• Evaluation of free energy landscapes from manipulation experiments
• Internal protein dynamics shifts the distance to the mechanical transition state

Cited by in corpus (6)

• Stochastic thermodynamics, fluctuation theorems, and molecular machines
• Direction dependent mechanical unfolding and Green Fluorescent Protein as a force sensor
• A structure-based model fails to probe the mechanical unfolding pathways of the titin I27 domain
• Mechanical resistance in unstructured proteins
• Pathways of mechanical unfolding of FnIII_{10}: low force intermediates
• Markov modeling of peptide folding in the presence of protein crowders