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We present a method to obtain numerically accurate values of configurational free energies of semiflexible macromolecular systems, based on the technique of thermodynamic integration combined with normal-mode analysis of a reference system…

Biomolecules · Quantitative Biology 2018-10-17 Stefan M. Giovan , Robert G. Scharein , Andreas Hanke , Stephen D. Levene

The mechanical unfolding of an engineered protein composed of eight domains of Ig27 is investigated by using atomic force microscopy. Exploiting a fluctuation relation, the equilibrium free energy as a function of the molecule elongation is…

Soft Condensed Matter · Physics 2008-05-29 A. Imparato , F. Sbrana , M. Vassalli

One of the most intriguing results of single molecule experiments on proteins and nucleic acids is the discovery of functional heterogeneity: the observation that complex cellular machines exhibit multiple, biologically active…

Biomolecules · Quantitative Biology 2022-10-12 Michael Hinczewski , Changbong Hyeon , D. Thirumalai

We establish a framework for assessing whether the transition state location of a biopolymer, which can be inferred from single molecule pulling experiments, corresponds to the ensemble of structures that have equal probability of reaching…

Soft Condensed Matter · Physics 2015-05-27 Greg Morrison , Changbong Hyeon , Michael Hinczewski , D. Thirumalai

Single-molecule pulling techniques have emerged as versatile tools for probing the noncovalent forces holding together the secondary and tertiary structure of macromolecules. They also constitute a way to study at the single-molecule level…

Biological Physics · Physics 2013-02-19 Ignacio Franco , Mark A. Ratner , George C. Schatz

In this report I discuss fluctuation theorems and transient violations of the second law of thermodynamics in small systems. Special emphasis is placed on free-energy recovery methods in the framework of non-equilibrium single-molecule…

Statistical Mechanics · Physics 2015-06-24 F. Ritort

The impact of leading collective electronic fluctuations on a free energy of a prototype 1D model for molecular systems is considered within the recently developed Fluctuating Local Field (FLF) approach. The FLF method is a non-perturbative…

Strongly Correlated Electrons · Physics 2022-01-14 Yana S. Lyakhova , Evgeny A. Stepanov , Alexey N. Rubtsov

We investigate the possibility of extending the notion of temperature in a stochastic model for the RNA/protein folding driven out of equilibrium. We simulate the dynamics of a small RNA hairpin subject to an external pulling force, which…

Statistical Mechanics · Physics 2021-08-02 Marco Ancona , Alessandro Bentivoglio , Michele Caraglio , Giuseppe Gonnella , Alessandro Pelizzola

In this work, we propose two models of coupled harmonic oscillators under Brownian motion to computationally study the applications of fluctuation theorems. This paper also illustrates how to analytically calculate free energy differences…

Statistical Mechanics · Physics 2025-09-03 Julián David Jiménez-Paz , José Daniel Muñoz-Castaño

Non-coding RNA sequences play a great role in controlling a number of cellular functions, thus raising the need to understand their complex conformational dynamics in quantitative detail. In this perspective, we first show that single…

Biomolecules · Quantitative Biology 2012-11-29 Jong-Chin Lin , Changbong Hyeon , D. Thirumalai

Fluctuation theorems, such as the Jarzynski equality and the Crooks relation, are effective tools connecting non-equilibrium work statistics and equilibrium free energy differences. However, detailed hands-on, reproducible protocols for…

Heterogeneity in biological molecules, resulting in molecule-to-molecule variations in their dynamics and function, is an emerging theme. To elucidate the consequences of heterogeneous behavior at the single molecule level, we propose an…

Biological Physics · Physics 2017-01-24 Changbong Hyeon , Michael Hinczewski , D. Thirumalai

We apply Kramers theory to investigate the dissociation of multiple bonds under mechanical force and interpret experimental results for the unfolding/refolding force distributions of an RNA hairpin pulled at different loading rates using…

Soft Condensed Matter · Physics 2009-11-11 M. Manosas , D. Collin , F. Ritort

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…

Statistical Mechanics · Physics 2007-05-23 A. Imparato , L. Peliti

The freely jointed chain is often applied to model the thermodynamics of single polymer chains, but the traditional formulation of the model lacks internal energy changes due to bond stretching. For this reason, the extensible freely…

Statistical Mechanics · Physics 2026-05-13 Michael R. Buche

Single molecule pulling experiments provide information about interactions in biomolecules that cannot be obtained by any other method. However, the reconstruction of the molecule's free energy profile from the experimental data is still a…

Soft Condensed Matter · Physics 2009-11-10 Oliver Braun , Andreas Hanke , Udo Seifert

Single-molecule experiments with optical tweezers have become an important tool to study the properties and mechanisms of biological systems, such as cells and nucleic acids. In particular, force unzipping experiments have been used to…

Biological Physics · Physics 2019-07-22 Marc Rico-Pasto , Isabel Pastor , Felix Ritort

Single-molecule experiments provide new insights into biological processes hitherto not accessible by measurements performed on bulk systems. We report on a study of the kinetics of a triple-branch DNA molecule with four conformational…

Biological Physics · Physics 2011-06-13 Sandra Engel , Anna Alemany , Nuria Forns , Philipp Maass , Felix Ritort

Using a one-dimensional macromolecule in aqueous solution as an illustration, we demonstrate that the relative entropy from information theory, $\sum_k p_k\ln(p_k/p_k^*)$, has a natural role in the energetics of equilibrium and…

Mathematical Physics · Physics 2007-05-23 Hong Qian

By exerting mechanical force it is possible to unfold/refold RNA molecules one at a time. In a small range of forces, an RNA molecule can hop between the folded and the unfolded state with force-dependent kinetic rates. Here, we introduce a…

Biological Physics · Physics 2012-08-27 M. Manosas , J. -D. Wen , P. T. X. Li , S. B. Smith , C. Bustamante , I. Tinoco, , F. Ritort