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

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.Comment: Latex manuscript, 20 pages, 23 figures, submitted to Physical Review

Reconstructing the free energy landscape of a mechanically unfolded model protein

The equilibrium free energy landscape of an off-lattice model protein as a function of an internal (reaction) coordinate is reconstructed from out-of-equilibrium mechanical unfolding manipulations. This task is accomplished via two independent methods: by employing an extended version of the Jarzynski equality (EJE) and the protein inherent structures (ISs). In a range of temperatures around the ``folding transition'' we find a good quantitative agreement between the free energies obtained via EJE and IS approaches. This indicates that the two methodologies are consistent and able to reproduce equilibrium properties of the examined system. Moreover, for the studied model the structural transitions induced by pulling can be related to thermodynamical aspects of folding

Surface tension in bilayer membranes with fixed projected area

We study the elastic response of bilayer membranes with fixed projected area to both stretching and shape deformations. A surface tension is associated to each of these deformations. By using model amphiphilic membranes and computer simulations, we are able to observe both the types of deformation, and thus, both the surface tensions, related to each type of deformation, are measured for the same system. These surface tensions are found to assume different values in the same bilayer membrane: in particular they vanish for different values of the projected area. We introduce a simple theory which relates the two quantities and successfully apply it to the data obtained with computer simulations

Probability density functions of work and heat near the stochastic resonance of a colloidal particle

We study experimentally and theoretically the probability density functions of the injected and dissipated energy in a system of a colloidal particle trapped in a double well potential periodically modulated by an external perturbation. The work done by the external force and the dissipated energy are measured close to the stochastic resonance where the injected power is maximum. We show a good agreement between the probability density functions exactly computed from a Langevin dynamics and the measured ones. The probability density function of the work done on the particle satisfies the fluctuation theorem

Minimal Detectable and Identifiable Biases for quality control

The Minimal Detectable Bias (MDB) is an important diagnostic tool in data quality control. The MDB is traditionally computed for the case of testing the null hypothesis against a single alternative hypothesis. In the actual practice of statistical testing and data quality control, however, multiple alternative hypotheses are considered. We show that this has two important consequences for one's interpretation and use of the popular MDB. First, we demonstrate that care should be exercised in using the single-hypothesis-based MDB for the multiple hypotheses case. Second, we show that for identification purposes, not the MDB, but the Minimal Identifiable Bias (MIB) should be used as the proper diagnostic tool. We analyse the circumstances that drive the differences between the MDBs and MIBs, show how they can be computed using Monte Carlo simulation and illustrate by means of examples the significant differences that one can experience between detectability and identifiability

Energetics and performance of a microscopic heat engine based on exact calculations of work and heat distributions

We investigate a microscopic motor based on an externally controlled two-level system. One cycle of the motor operation consists of two strokes. Within each stroke, the two-level system is in contact with a given thermal bath and its energy levels are driven with a constant rate. The time evolution of the occupation probabilities of the two states are controlled by one rate equation and represent the system's response with respect to the external driving. We give the exact solution of the rate equation for the limit cycle and discuss the emerging thermodynamics: the work done on the environment, the heat exchanged with the baths, the entropy production, the motor's efficiency, and the power output. Furthermore we introduce an augmented stochastic process which reflects, at a given time, both the occupation probabilities for the two states and the time spent in the individual states during the previous evolution. The exact calculation of the evolution operator for the augmented process allows us to discuss in detail the probability density for the performed work during the limit cycle. In the strongly irreversible regime, the density exhibits important qualitative differences with respect to the more common Gaussian shape in the regime of weak irreversibility.Comment: 21 pages, 7 figure

Discrete Breathers in a Realistic Coarse-Grained Model of Proteins

We report the results of molecular dynamics simulations of an off-lattice protein model featuring a physical force-field and amino-acid sequence. We show that localized modes of nonlinear origin (discrete breathers) emerge naturally as continuations of a subset of high-frequency normal modes residing at specific sites dictated by the native fold. In the case of the small $\beta$-barrel structure that we consider, localization occurs on the turns connecting the strands. At high energies, discrete breathers stabilize the structure by concentrating energy on few sites, while their collapse marks the onset of large-amplitude fluctuations of the protein. Furthermore, we show how breathers develop as energy-accumulating centres following perturbations even at distant locations, thus mediating efficient and irreversible energy transfers. Remarkably, due to the presence of angular potentials, the breather induces a local static distortion of the native fold. Altogether, the combination of this two nonlinear effects may provide a ready means for remotely controlling local conformational changes in proteins.Comment: Submitted to Physical Biolog