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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

Detecting conformational transitions in molecular systems is key to understanding biological processes. Here, we investigate the force variance in single-molecule pulling experiments as an indicator of molecular folding transitions. We…

Statistical Mechanics · Physics 2023-09-13 Marc Rico , Felix Ritort

Most single-molecule studies derive the kinetic rates of native, intermediate, and unfolded states from equilibrium hopping experiments. Here, we apply Kramers kinetic diffusive model to derive the force-dependent kinetic rates of…

Soft Condensed Matter · Physics 2022-04-13 Marc Rico-Pasto , Anna Alemany , Felix Ritort

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

The sequence-dependent folding landscapes of nucleic acid hairpins reflect much of the complexity of biomolecular folding. Folding trajectories, generated using single molecule force clamp experiments by attaching semiflexible polymers to…

Soft Condensed Matter · Physics 2009-11-13 Changbong Hyeon , Greg Morrison , D. Thirumalai

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

Single-molecule force spectroscopy has opened a new field of research in molecular biophysics and biochemistry. Pulling experiments on individual proteins permit us to monitor conformational transitions with high temporal resolution and…

Soft Condensed Matter · Physics 2021-11-23 M. Rico-Pasto , A. Zaltron , F. Ritort

Feedback traps are tools for trapping and manipulating single charged objects, such as molecules in solution. An alternative to optical tweezers and other single-molecule techniques, they use feedback to counteract the Brownian motion of a…

Statistical Mechanics · Physics 2017-01-24 Momčilo Gavrilov , John Bechhoefer

In recent years single molecule force spectroscopy has opened a new avenue to provide profiles of the complex energy landscape of biomolecules. In this field, quantitative analyses of the data employing sound theoretical models, have played…

Biomolecules · Quantitative Biology 2015-01-15 Changbong Hyeon , Michael Hinczewski , D. Thirumalai

We present an extensive theoretical investigation of the mechanical unzipping of double-stranded DNA under the influence of an applied force. In the limit of long polymers, there is a thermodynamic unzipping transition at a critical force…

Soft Condensed Matter · Physics 2009-11-07 David K. Lubensky , David R. Nelson

Single molecule mechanical unfolding experiments are beginning to provide profiles of the complex energy landscape of biomolecules. In order to obtain reliable estimates of the energy landscape characteristics it is necessary to combine the…

Soft Condensed Matter · Physics 2009-11-11 Changbong Hyeon , D. Thirumalai

Biological macromolecules have complex and non-trivial energy landscapes, endowing them a unique conformational adaptability and diversity in function. Hence, understanding the processes of elasticity and dissipation at the nanoscale is…

Soft Condensed Matter · Physics 2009-11-11 Bhavin S. Khatri , Masaru Kawakami , Katherine Byrne , D. Alastair Smith , Tom C. B. McLeish

The process of protein folding from an unfolded state to a biologically active, folded conformation is governed by many parameters e.g the sequence of amino acids, intermolecular interactions, the solvent, temperature and chaperon…

Soft Condensed Matter · Physics 2010-10-19 Pragya Shukla

The remarkable accuracy and versatility of single-molecule techniques make possible new measurements that are not feasible in bulk assays. Among these, the precise estimation of folding free energies using fluctuation theorems in…

Biomolecules · Quantitative Biology 2019-12-19 Aurelien Severino , Alvaro Martinez Monge , Paolo Rissone , Felix Ritort

We theoretically investigate the extractable work in single molecule unfolding-folding experiments with applied feedback. Using a simple two-state model, we obtain a description of the full work distribution, from discrete to continuous…

We investigate irreversibility and dissipation in single molecules that cooperatively fold/unfold in a two state manner under the action of mechanical force. We apply path thermodynamics to derive analytical expressions for the average…

Statistical Mechanics · Physics 2009-02-25 Maria Manosas , Alessandro Mossa , Nuria Forns , Josep Maria Huguet , Felix Ritort

We investigate unfolding/folding force kinetics in DNA hairpins exhibiting two and three states with newly designed short dsDNA handles (29 bp) using optical tweezers. We show how the higher stiffness of the molecular setup moderately…

Statistical Mechanics · Physics 2011-05-25 N. Forns , S. de Lorenzo , M. Manosas , K. Hayashi , J. M. Huguet , F. Ritort

We have developed a new extended replica exchange method to study thermodynamics of a system in the presence of external force. Our idea is based on the exchange between different force replicas to accelerate the equilibrium process. We…

Biomolecules · Quantitative Biology 2009-11-13 Maksim Kouza , Chin-Kun Hu , Mai Suan Li

Molecular simulations of the forced unfolding and refolding of biomolecules or molecular complexes allow to gain important kinetic, structural and thermodynamic information about the folding process and the underlying energy landscape. In…

Soft Condensed Matter · Physics 2021-05-26 Marco Oestereich , Jürgen Gauss , Gregor Diezemann

Recent single-molecule pulling experiments have shown how it is possible to manipulate RNA molecules using optical tweezers force microscopy. We investigate a minimal model for the experimental setup which includes a RNA molecule connected…

Statistical Mechanics · Physics 2009-11-10 Maria Manosas , Felix Ritort
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