Lattice Model Studies of Force-Induced Unfolding of Proteins

Klimov, Dmitri K.; Thirumalai, D.

doi:10.1021/jp0101561

Cited by 28 publications

(35 citation statements)

References 22 publications

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“…In the presence of a constant f and assuming a rapid alignment of the end-to-end vector ជ R along the force direction, the total energy of the polypeptide is E f ϭ E Ϫ fR. We calculated f-dependent thermodynamic quantities by using a version of the multiple histogram method, in which both temperature T and f are varied (18).…”

Section: Methodsmentioning

confidence: 99%

Multiple stepwise refolding of immunoglobulin domain I27 upon force quench depends on initial conditions

Klimov

et al. 2005

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

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Section: Methodsmentioning

confidence: 99%

Multiple stepwise refolding of immunoglobulin domain I27 upon force quench depends on initial conditions

Klimov

et al. 2005

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

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“…(10). Thus, the computation of the FEC is not dependent on whether Z or R 2 ⊥ is used in determining the self-consistent equation.…”

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Stretching Homopolymers

et al. 2007

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Force induced stretching of polymers is important in a variety of contexts. We have used theory and simulations to describe the response of homopolymers, with N monomers, to force (f ) in good and poor solvents. In good solvents and for sufficiently large N we show, in accord with scaling predictions, that the mean extension along the f axis Z ∼ f for small f , and Z ∼ f 2 3 (the Pincus regime) for intermediate values of f . The theoretical predictions for Z as a function of f are in excellent agreement with simulations for N = 100 and 1600. However, even with N = 1600, the expected Pincus regime is not observed due to the the breakdown of the assumptions in the blob picture for finite N . We predict the Pincus scaling in a good solvent will be observed for N 10 5 . The forcedependent structure factors for a polymer in a poor solvent show that there are a hierarchy of structures, depending on the nature of the solvent. For a weakly hydrophobic polymer, various structures (ideal conformations, self-avoiding chains, globules, and rods) emerge on distinct length scales as f is varied. A strongly hydrophobic polymer remains globular as long as f is less than a critical value f c . Above f c , an abrupt first order transition to a rod-like structure occurs. Our predictions can be tested using single molecule experiments.1 arXiv:0705.3029v1 [cond-mat.soft]

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“…In concert with theoretical studies (9, 14, 15), these measurements can be used to construct the free energy landscape of proteins and RNA. For example, we have shown that, by using dynamics of nonequilibrium stretching experiments, one can infer the distribution of free energy barriers in the absence of force (16). Measurement of distribution of free energy barriers requires following time-dependent events, at the single molecule level, when unfolding is induced by force.…”

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Can energy landscape roughness of proteins and RNA be measured by using mechanical unfolding experiments?

Hyeon

Thirumalai²

2003

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

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By considering temperature effects on the mechanical unfolding rates of proteins and RNA, whose energy landscape is rugged, the question posed in the title is answered in the affirmative. Adopting a theory by Zwanzig [Zwanzig, R. (1988) Proc. Natl. Acad. Sci. USA 85, 2029 -2030], we show that, because of roughness characterized by an energy scale , the unfolding rate at constant force is retarded. Similarly, in nonequilibrium experiments done at constant loading rates, the most probable unfolding force increases because of energy landscape roughness. The effects are dramatic at low temperatures. Our analysis suggests that, by using temperature as a variable in mechanical unfolding experiments of proteins and RNA, the ruggedness energy scale , can be directly measured.V isualizing folding of proteins (1-3) and RNA (2) in terms of the underlying energy landscape has been fruitful in anticipating diverse folding scenarios. The polymeric nature of these biomolecules and the presence of multiple energy scales associated with the building blocks of proteins and RNA make their underlying energy landscape rugged. By rugged, we mean that the energy landscape consists of several minima separated by barriers of varying heights. To understand the diversity of the folding pathways, it is necessary to determine the characteristics of the energy landscape experimentally.It is difficult to represent the large dimensional space of the energy landscape in terms of a few parameters. However, the ruggedness of the energy landscape can be described in terms of an energy scale regardless of the precise nature of the underlying reaction coordinate. Within the energy landscape picture, it is clear that rapid folding to the native conformation on a finite (biologically relevant) time scale is unlikely if ͞k B

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Lattice Model Studies of Force-Induced Unfolding of Proteins

Cited by 28 publications

References 22 publications

Multiple stepwise refolding of immunoglobulin domain I27 upon force quench depends on initial conditions

Multiple stepwise refolding of immunoglobulin domain I27 upon force quench depends on initial conditions

Stretching Homopolymers

Can energy landscape roughness of proteins and RNA be measured by using mechanical unfolding experiments?

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