Exactness of the cluster variation method and factorization of the equilibrium probability for the Wako-Saito-Munoz-Eaton model of protein folding

I study the properties of the equilibrium probability distribution of a protein folding model originally introduced by Wako and Saito, and later reconsidered by Munoz and Eaton. The model is a one-dimensional model with binary variables and many-body, long-range interactions, which has been solved exactly through a mapping to a two-dimensional model of binary variables with local constraints. Here I show that the equilibrium probability of this two-dimensional model factors into the product of local cluster probabilities, each raised to a suitable exponent. The clusters involved are single sites, nearest-neighbour pairs and square plaquettes, and the exponents are the coefficients of the entropy expansion of the cluster variation method. As a consequence, the cluster variation method is exact for this model.Comment: 14 pages, 1 figur

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

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

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

The Phase Diagram of the Gonihedric 3d Ising Model via CVM

We use the cluster variation method (CVM) to investigate the phase structure of the 3d gonihedric Ising actions defined by Savvidy and Wegner. The geometrical spin cluster boundaries in these systems serve as models for the string worldsheets of the gonihedric string embedded in ${\bf Z}^3$. The models are interesting from the statistical mechanical point of view because they have a vanishing bare surface tension. As a result the action depends only on the angles of the discrete surface and not on the area, which is the antithesis of the standard 3d Ising model. The results obtained with the CVM are in good agreement with Monte Carlo simulations for the critical temperatures and the order of the transition as the self-avoidance coupling $\kappa$ is varied. The value of the magnetization critical exponent $\beta = 0.062 \pm 0.003$, calculated with the cluster variation--Pad\`e approximant method, is also close to the simulation results.Comment: 8 pages text (LaTex) + 3 eps figures bundled together with uufile

Downhill versus two-state protein folding in a statistical mechanical model

The authors address the problem of downhill protein folding in the framework of a simple statistical mechanical model, which allows an exact solution for the equilibrium and a semianalytical treatment of the kinetics. Focusing on protein 1BBL, a candidate for downhill folding behavior, and comparing it to the WW domain of protein PIN1, a two-state folder of comparable size, the authors show that there are qualitative differences in both the equilibrium and kinetic properties of the two molecules. However, the barrierless scenario which would be expected if 1BBL were a true downhill folder is observed only at low enough temperature.Comment: 20 pages, 13 figure

Rigorous results on the local equilibrium kinetics of a protein folding model

A local equilibrium approach for the kinetics of a simplified protein folding model, whose equilibrium thermodynamics is exactly solvable, was developed in [M. Zamparo and A. Pelizzola, Phys. Rev. Lett. 97, 068106 (2006)]. Important properties of this approach are (i) the free energy decreases with time, (ii) the exact equilibrium is recovered in the infinite time limit, (iii) the equilibration rate is an upper bound of the exact one and (iv) computational complexity is polynomial in the number of variables. Moreover, (v) this method is equivalent to another approximate approach to the kinetics: the path probability method. In this paper we give detailed rigorous proofs for the above results.Comment: 25 pages, RevTeX 4, to be published in JSTA

Cluster variation - Pade` approximants method for the simple cubic Ising model

The cluster variation - Pade` approximant method is a recently proposed tool, based on the extrapolation of low/high temperature results obtained with the cluster variation method, for the determination of critical parameters in Ising-like models. Here the method is applied to the three-dimensional simple cubic Ising model, and new results, obtained with an 18-site basic cluster, are reported. Other techniques for extracting non-classical critical exponents are also applied and their results compared with those by the cluster variation - Pade` approximant method.Comment: 8 RevTeX pages, 3 PostScript figure

Equilibrium properties and force-driven unfolding pathways of RNA molecules

The mechanical unfolding of a simple RNA hairpin and of a 236--bases portion of the Tetrahymena thermophila ribozyme is studied by means of an Ising--like model. Phase diagrams and free energy landscapes are computed exactly and suggest a simple two--state behaviour for the hairpin and the presence of intermediate states for the ribozyme. Nonequilibrium simulations give the possible unfolding pathways for the ribozyme, and the dominant pathway corresponds to the experimentally observed one.Comment: Main text + appendix, to appear in Phys. Rev. Let

Effects of confinement on thermal stability and folding kinetics in a simple Ising-like model

In cellular environment, confinement and macromulecular crowding play an important role on thermal stability and folding kinetics of a protein. We have resorted to a generalized version of the Wako-Saito-Munoz-Eaton model for protein folding to study the behavior of six different protein structures confined between two walls. Changing the distance 2R between the walls, we found, in accordance with previous studies, two confinement regimes: starting from large R and decreasing R, confinement first enhances the stability of the folded state as long as this is compact and until a given value of R; then a further decrease of R leads to a decrease of folding temperature and folding rate. We found that in the low confinement regime both unfolding temperatures and logarithm of folding rates scale as R-{\gamma} where {\gamma} values lie in between 1.42 and 2.35