Free energy landscape of mechanically unfolded model proteins: extended Jarzinsky versus inherent structure reconstruction

TL;DR

This study compares methods for reconstructing the free energy landscape of model proteins under mechanical unfolding, revealing good agreement with equilibrium techniques and insights into folding thermodynamics and kinetics.

Contribution

It introduces an extended Jarzynski equality approach and compares it with inherent structure formalism for free energy landscape reconstruction.

Findings

Good agreement between methods around folding transition temperature.

Mechanical unfolding relates to thermodynamics for well-folded sequences.

Landscape profile estimates native state lifetimes across temperature range.

Abstract

The equilibrium free energy landscape of off-lattice model heteropolymers as a function of an internal coordinate, namely the end-to-end distance, is reconstructed from out-of-equilibrium steered molecular dynamics data. This task is accomplished via two independent methods: by employing an extended version of the Jarzynski equality (EJE) and the inherent structure (IS) formalism. A comparison of the free energies estimated with these two schemes with equilibrium results obtained via the umbrella sampling technique reveals a good quantitative agreement among all the approaches in a range of temperatures around the ``folding transition'' for the two examined sequences. In particular, for the sequence with good foldability properties, the mechanically induced structural transitions can be related to thermodynamical aspects of folding. Moreover, for the same sequence the knowledge of the landscape profile allows for a good estimation of the life times of the native configuration for temperatures ranging from the folding to the collapse temperature. For the random sequence, mechanical and thermal unfolding appear to follow different paths along the landscape.