Mechanical unfolding and refolding pathways of ubiquitin

Mechanical unfolding and refolding of ubiquitin are studied by Monte Carlo simulations of a Go model with binary variables. The exponential dependence of the time constants on the force is verified, and folding and unfolding lengths are computed, with good agreement with experimental results. Furthermore, the model exhibits intermediate kinetic states, as observed in experiments. Unfolding and refolding pathways and intermediate states, obtained by tracing single secondary structure elements, are consistent with simulations of previous all-atom models and with the experimentally observed step sizes

Evaluation of free energy landscapes from manipulation experiments

A fluctuation relation, which is an extended form of the Jarzynski equality, is introduced and discussed. We show how to apply this relation in order to evaluate the free energy landscape of simple systems. These systems are manipulated by varying the external field coupled with a systems' internal characteristic variable. Two different manipulation protocols are here considered: in the first case the external field is a linear function of time, in the second case it is a periodic function of time. While for simple mean field systems both the linear protocol and the oscillatory protocol provide a reliable estimate of the free energy landscape, for a simple model ofhomopolymer the oscillatory protocol turns out to be not reliable for this purpose. We then discuss the possibility of application of the method here presented to evaluate the free energy landscape of real systems, and the practical limitations that one can face in the realization of an experimental set-up

Work probability distribution in systems driven out of equilibrium

We derive the differential equation describing the time evolution of the work probability distribution function of a stochastic system which is driven out of equilibrium by the manipulation of a parameter. We consider both systems described by their microscopic state or by a collective variable which identifies a quasiequilibrium state. We show that the work probability distribution can be represented by a path integral, which is dominated by ``classical'' paths in the large system size limit. We compare these results with simulated manipulation of mean-field systems. We discuss the range of applicability of the Jarzynski equality for evaluating the system free energy using these out-of-equilibrium manipulations. Large fluctuations in the work and the shape of the work distribution tails are also discussed

The distribution function of entropy flow in stochastic systems

We obtain a simple direct derivation of the differential equation governing the entropy flow probability distribution function of a stochastic system first obtained by Lebowitz and Spohn. Its solution agrees well with the experimental results of Tietz et al [2006 {\it Phys. Rev. Lett.} {\bf 97} 050602]. A trajectory-sampling algorithm allowing to evaluate the entropy flow distribution function is introduced and discussed. This algorithm turns out to be effective at finite times and in the case of time-dependent transition rates, and is successfully applied to an asymmetric simple exclusion process

Heat flow in chains driven by thermal noise

We consider the large deviation function for a classical harmonic chain composed of N particles driven at the end points by heat reservoirs, first derived in the quantum regime by Saito and Dhar and in the classical regime by Saito and Dhar and Kundu et al. Within a Langevin description we perform this calculation on the basis of a standard path integral calculation in Fourier space. The cumulant generating function yielding the large deviation function is given in terms of a transmission Green's function and is consistent with the fluctuation theorem. We find a simple expression for the tails of the heat distribution which turn out to decay exponentially. We, moreover, consider an extension of a single particle model suggested by Derrida and Brunet and discuss the two-particle case. We also discuss the limit for large N and present a closed expression for the cumulant generating function. Finally, we present a derivation of the fluctuation theorem on the basis of a Fokker-Planck description. This result is not restricted to the harmonic case but is valid for a general interaction potential between the particles.Comment: Latex: 26 pages and 9 figures, appeared in J. Stat. Mech. P04005 (2012

Direction dependent mechanical unfolding and Green Fluorescent Protein as a force sensor

An Ising--like model of proteins is used to investigate the mechanical unfolding of the Green Fluorescent Protein along different directions. When the protein is pulled from its ends, we recover the major and minor unfolding pathways observed in experiments. Upon varying the pulling direction, we find the correct order of magnitude and ranking of the unfolding forces. Exploiting the direction dependence of the unfolding force at equilibrium, we propose a force sensor whose luminescence depends on the applied force.Comment: to appear in Phys Rev

Out-of-equilibrium versus dynamical and thermodynamical transitions for a model protein

Equilibrium and out-of-equilibrium transitions of an off-lattice protein model have been identified and studied. In particular, the out-of-equilibrium dynamics of the protein undergoing mechanical unfolding is investigated, and by using a work fluctuation relation, the system free energy landscape is evaluated. Three different structural transitions are identified along the unfolding pathways. Furthermore, the reconstruction of the the free and potential energy profiles in terms of inherent structure formalism allows us to put in direct correspondence these transitions with the equilibrium thermal transitions relevant for protein folding/unfolding. Through the study of the fluctuations of the protein structure at different temperatures, we identify the dynamical transitions, related to configurational rearrangements of the protein, which are precursors of the thermal transitions.Comment: Proceedings of the "YKIS 2009 : Frontiers in Nonequilibrium Physics" conference in Kyoto, August 2009. To appear in Progress of Theoretical Physics Supplemen

Protein mechanical unfolding: a model with binary variables

A simple lattice model, recently introduced as a generalization of the Wako--Sait\^o model of protein folding, is used to investigate the properties of widely studied molecules under external forces. The equilibrium properties of the model proteins, together with their energy landscape, are studied on the basis of the exact solution of the model. Afterwards, the kinetic response of the molecules to a force is considered, discussing both force clamp and dynamic loading protocols and showing that theoretical expectations are verified. The kinetic parameters characterizing the protein unfolding are evaluated by using computer simulations and agree nicely with experimental results, when these are available. Finally, the extended Jarzynski equality is exploited to investigate the possibility of reconstructing the free energy landscape of proteins with pulling experiments

Efficiency of molecular machines with continuous phase space

We consider a molecular machine described as a Brownian particle diffusing in a tilted periodic potential. We evaluate the absorbed and released power of the machine as a function of the applied molecular and chemical forces, by using the fact that the times for completing a cycle in the forward and the backward direction have the same distribution, and that the ratio of the corresponding splitting probabilities can be simply expressed as a function of the applied force. We explicitly evaluate the efficiency at maximum power for a simple sawtooth potential. We also obtain the efficiency at maximum power for a broad class of 2-D models of a Brownian machine and find that loosely coupled machines operate with a smaller efficiency at maximum power than their strongly coupled counterparts.Comment: To appear in EP