Model Energy Landscapes and the Force-Induced Dissociation of Ligand-Receptor Bonds

Strunz, Torsten; Oroszlan, Krisztina; Schumakovitch, Irina; Güntherodt, H.-J.; Hegner, Martin

doi:10.1016/s0006-3495(00)76375-2

Cited by 147 publications

(121 citation statements)

References 30 publications

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“…(iii) Assume that the model (28), (29) is applicable and deduce its model parameters µ = (λ, α) from the slope and the axis intercept of the straight line as detailed e.g. in [1,12,15,16,35]. We have applied this procedure to each of the 10000 experiments in Fig.…”

Section: B Illustration For Computer Generated Datamentioning

confidence: 99%

Single-molecule force spectroscopy: Practical limitations beyond Bell’s model

Getfert

Evstigneev

Reimann

2009

Physica A: Statistical Mechanics and its Applications

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Single-molecule force spectroscopy experiments, as well as a number of other physical systems, are governed by thermally activated transitions out of a metastable state under the action of a steadily increasing external force. The main observable in such experiments is the distribution of the forces, at which the escape events occur. The challenge in interpreting the experimental data is to relate them to the microscopic system properties. We work out a maximum likelihood approach and show that it is the optimal method to tackle this problem. When fitting actual experimental data it is unavoidable to assume some functional form for the force-dependent escape rate. We consider a quite general and common such functional form and demonstrate by means of data from a realistic computer experiment that the maximum number of fit parameters that can be determined reliably is three. They are related to the force-free escape rate and the position and height of the activation barrier. Furthermore, the results for the first two of these fit parameters show little dependence on the assumption about the manner in which the barrier decreases with the applied force, while the last one, the barrier height in the absence of force, depends strongly on this assumption.

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Section: B Illustration For Computer Generated Datamentioning

confidence: 99%

Single-molecule force spectroscopy: Practical limitations beyond Bell’s model

Getfert

Evstigneev

Reimann

2009

Physica A: Statistical Mechanics and its Applications

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“…Let t 0 be the time at which the inner barrier disappears, defined as t 0 = E A /(rx A ), and let t max be the maximum time for the integration of the evolution equations (10) and (11). Thus, with our parameter choice, we took t max < t 0 .…”

Section: Resultsmentioning

confidence: 99%

“…In this case, a slightly modified version of eqs. (10) and (11) has to be considered to take into account the disappearing of the barrier (x A , E A ) at t = t 0 . The outcome for q(f, r) is similar to that shown in fig.…”

Section: Resultsmentioning

confidence: 99%

“…In the unzipping experiments, tertiary contacts may lead to the appearance of kinetic barriers where the unzipping process momentarily stops [3,4]. In this situation, overcoming these barriers bears some analogy with the breakup of molecular adhesion studied in a number of experiments [9,10] which have been recently reanalyzed theoretically [11,12,13]. In the present paper, we wish to understand some features of the experiments on RNA unzipping in the light of this theory, in order to highlight what information one is able to collect from the unzipping kinetics on the position and the height of the barriers due to the tertiary structure.…”

Section: Introductionmentioning

confidence: 99%

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Kinetic barriers in RNA unzipping

Imparato

Peliti

2004

Eur. Phys. J. B

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Abstract. We consider a simple model for the unfolding of RNA tertiary structure under dynamic loading. The opening of such a structure is regarded as a two step process, each corresponding to the overcoming of a single energy barrier. The resulting two-barrier energy landscape accounts for the dependence of the unfolding kinetics on the pulling rate. Furthermore at intermediate force, the two barriers cannot be distinguished by the analysis of the opening kinetic, which turns out to be dominated by a single macrobarrier, whose properties depend non-trivially on the two single barriers. Our results suggest that in pulling experiments on RNA molecule containing tertiary structures, the details of the single kinetic barriers can only be obtained using a low pulling rate value, or in the high force regime.

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“…As a result, analytical studies of forceinduced molecular transitions in such systems usually focus on the effective rate k eff ðFÞ at constant force (16,17). An expression for the quantity of relevance to force-ramp experiments-the most probable rupture force F*ðV Þ at pulling speed V-has been attempted empirically (17): the single-barrier rate kðFÞ was replaced by the multiple-barrier rate k eff ðFÞ in the single-barrier version of the expression for F*ðV Þ.…”

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confidence: 99%

A transformation for the mechanical fingerprints of complex biomolecular interactions

Zhang

Dudko

2013

Proc. Natl. Acad. Sci. U.S.A.

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Biological processes are carried out through molecular conformational transitions, ranging from the structural changes within biomolecules to the formation of macromolecular complexes and the associations between the complexes themselves. These transitions cover a vast range of timescales and are governed by a tangled network of molecular interactions. The resulting hierarchy of interactions, in turn, becomes encoded in the experimentally measurable "mechanical fingerprints" of the biomolecules, their forceextension curves. However, how can we decode these fingerprints so that they reveal the kinetic barriers and the associated timescales of a biological process? Here, we show that this can be accomplished with a simple, model-free transformation that is general enough to be applicable to molecular interactions involving an arbitrarily large number of kinetic barriers. Specifically, the transformation converts the mechanical fingerprints of the system directly into a map of force-dependent rate constants. This map reveals the kinetics of the multitude of rate processes in the system beyond what is typically accessible to direct measurements. With the contributions from individual barriers to the interaction network now "untangled", the map is straightforward to analyze in terms of the prominent barriers and timescales. Practical implementation of the transformation is illustrated with simulated biomolecular interactions that comprise different patterns of complexity-from a cascade of activation barriers to competing dissociation pathways.complex interactions | single molecule | force spectroscopy | kinetic rate C onformational transitions in biological macromoleculessuch as the folding of nucleic acids and proteins or the binding of receptors and their ligands-usually serve as the mechanism that brings biomolecules into their working shape and enables their biological function (1). The conformational dynamics of a biomolecule are governed by its energy, which is described by a hypersurface-the energy landscape-in a space of the multitude of atomic coordinates. The energy landscapes of biological macromolecules are rough and hierarchical: the folded and unfolded (or bound and unbound) conformational states are often separated by a mountainous terrain of barriers (2-4). Remarkably, the prominent features of the landscape can be revealed by pulling the molecule apart: these features manifest themselves as nonmonotonic signatures-rips-in the force-extension curves of the molecule (5). Characteristics of the force-extension curves uniquely identify the biomolecule and thus serve as its "mechanical fingerprints" (6), in which the prominent barriers on the energy landscape are encoded. However, how can we decode the mechanical fingerprints to uncover the locations and heights of the barriers and the associated timescales of biomolecular motion (Fig. 1)? This is the central question addressed in the present paper.The realm of biomolecular interactions can be accessed in single-molecule force experiments, which apply a s...

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Model Energy Landscapes and the Force-Induced Dissociation of Ligand-Receptor Bonds

Cited by 147 publications

References 30 publications

Single-molecule force spectroscopy: Practical limitations beyond Bell’s model

Single-molecule force spectroscopy: Practical limitations beyond Bell’s model

Kinetic barriers in RNA unzipping

A transformation for the mechanical fingerprints of complex biomolecular interactions

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