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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

The dependence of the unfolding pathway of proteins on the pulling speed is investigated. This is done by introducing a simple one-dimensional chain comprising $N$ units, with different characteristic bistable free energies. These units…

Statistical Mechanics · Physics 2016-10-19 C. A. Plata , F. Cecconi , M. Chinappi , A. Prados

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

How DNA is mapped to functional proteins is a basic question of living matter. We introduce and study a physical model of protein evolution which suggests a mechanical basis for this map. Many proteins rely on large-scale motion to…

Biological Physics · Physics 2017-08-18 Tsvi Tlusty , Albert Libchaber , Jean-Pierre Eckmann

Neither of the two prevalent theories, namely thermodynamic stability and kinetic stability, provides a comprehensive understanding of protein folding. The thermodynamic theory is misleading because it assumes that free energy is the…

Biological Physics · Physics 2013-07-22 Ji Xu , Mengzhi Han , Ying Ren , Jinghai Li

Mechanical unfolding trajectories, generated by applying constant force in optical tweezer experiments, show that RNA hairpins and the P5abc subdomain of the group I intron unfold reversibly. We use coarse-grained Go-like models for RNA…

Biomolecules · Quantitative Biology 2009-11-11 Changbong Hyeon , D. Thirumalai

Understanding how monomeric proteins fold under in vitro conditions is crucial to describing their functions in the cellular context. Significant advances both in theory and experiments have resulted in a conceptual framework for describing…

Soft Condensed Matter · Physics 2010-07-20 D. Thirumalai , Edward P. O'Brien , Greg Morrison , Changbong Hyeon

In single-molecule force spectroscopy experiments, the dependence of the mean unfolding force on the loading rate is used for obtaining information about the energetic and dynamic properties of the system under study. However, it is crucial…

Biological Physics · Physics 2020-03-10 Rafayel Petrosyan

A microscopic theory of the free energy barriers and folding routes for minimally frustrated proteins is presented, greatly expanding on the presentation of the variational approach outlined previously [J. J. Portman, S. Takada, P. G.…

Soft Condensed Matter · Physics 2009-10-31 John J. Portman , Shoji Takada , Peter G. Wolynes

A central goal of protein-folding theory is to predict the stochastic dynamics of transition paths --- the rare trajectories that transit between the folded and unfolded ensembles --- using only thermodynamic information, such as a…

Biomolecules · Quantitative Biology 2018-08-09 William M. Jacobs , Eugene I. Shakhnovich

We develop a formalism for single molecule dynamic force spectroscopy to map the energy landscape of protein-protein complex ($P_1$$P_2$). The joint distribution $P(\tau_1,\tau_2)$ of unbinding lifetimes $\tau_1$ and $\tau_2$ measurable in…

Soft Condensed Matter · Physics 2009-11-11 V. Barsegov , D. Thirumalai

DNA hairpin molecules with periodic base sequences can be expected to exhibit a regular coarse-grained free energy landscape (FEL) as function of the number of open base pairs and applied mechanical force. Using a commonly employed model,…

Biological Physics · Physics 2013-12-17 Sandra Nostheide , Viktor Holubec , Petr Chvosta , Philipp Maass

A theoretical framework is developed to study the dynamics of protein folding. The key insight is that the search for the native protein conformation is influenced by the rate r at which external parameters, such as temperature, chemical…

Biomolecules · Quantitative Biology 2009-11-13 Gregg Lois , Jerzy Blawzdziewicz , Corey S. O'Hern

We present the results of an exact analysis of a model energy landscape of a protein to clarify the notion of the transition state and the physical meaning of the $\phi$ values determined in protein engineering experiments. We benchmark our…

Biomolecules · Quantitative Biology 2007-05-23 Iksoo Chang , Marek Cieplak , Jayanth R. Banavar , Amos Maritan

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…

Statistical Mechanics · Physics 2007-10-17 Alberto Imparato , Stefano Luccioli , Alessandro Torcini

In the current AFM experiments the distribution of unfolding times, P(t), is measured by applying a constant stretching force f_s from which the apparent unfolding rate is obtained. To describe the complexity of the underlying energy…

Soft Condensed Matter · Physics 2009-11-11 V. Barsegov , D. Klimov , D. Thirumalai

Mechanically induced unfolding of passive crosslinkers is a fundamental biological phenomenon encountered across the scales from individual macro-molecules to cytoskeletal actin networks. In this paper we study a conceptual model of…

Biological Physics · Physics 2015-01-08 M Caruel , J. -M Allain , L Truskinovsky

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

We present a statistical mechanics approach to the protein folding problem. We first review some of the basic properties of proteins, and introduce some physical models to describe their thermodynamics. These models rely on a random…

Disordered Systems and Neural Networks · Physics 2008-02-03 T. Garel , H. Orland , E. Pitard

The growing interest for comparing protein internal dynamics owes much to the realization that protein function can be accompanied or assisted by structural fluctuations and conformational changes. Analogously to the case of functional…

Biomolecules · Quantitative Biology 2012-12-19 C. Micheletti