Thermal effects in stretching of Go‐like models of titin and secondary structures

Cieplak, Marek; Hoang, Trinh Xuan; Robbins, Mark O.

doi:10.1002/prot.20081

Cited by 74 publications

(134 citation statements)

References 46 publications

(183 reference statements)

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“…The energy parameter, ǫ, is taken to be uniform and its effective value appears to be of order 900 K, at least for titin. The optimal folding temperature, T min , for I27 has been found to correspond to the reduced temperatureT = k B T /ǫ of 0.275 [9] (k B is the Boltzmann constant and T is temperature) which is close to the room temperature value ofT =0.3. In our stretching simulations, both ends of the protein are attached to harmonic springs of elastic constant k=0.12 ǫ/Å 2 which is close to the values corresponding to the elasticity of experimental cantilevers.…”

mentioning

confidence: 58%

“…Here, we analyse thermal unfolding within the topology-based model as implemented in Refs. [8] and [9].…”

mentioning

confidence: 99%

“…Mechanical stretching of this protein has been extensively studied in experiments involving atomic force microscopy [11][12][13] and there is also some information about its folding [14,15]. Furthermore, we have already studied it undergoing both processes through molecular dynamics simulations within the topology based model [9,[16][17][18].…”

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confidence: 99%

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Thermal unfolding of proteins

Cieplak

Sułkowska

2005

The Journal of Chemical Physics

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Thermal unfolding of proteins is compared to folding and mechanical stretching in a simple topology-based dynamical model. We define the unfolding time and demonstrate its low-temperature divergence. Below a characteristic temperature, contacts break at separate time scales and unfolding proceeds approximately in a way reverse to folding. Features in these scenarios agree with experiments and atomic simulations on titin.

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confidence: 58%

“…Here, we analyse thermal unfolding within the topology-based model as implemented in Refs. [8] and [9].…”

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confidence: 99%

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Thermal unfolding of proteins

Cieplak

Sułkowska

2005

The Journal of Chemical Physics

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“…We use the coarse-grained molecular dynamics modeling described in detail in refs (19,27,28). The native contacts between the C ␣ atoms in amino acids i and j separated by the distance r ij are described by the LennardJones potential V LJ ϭ 4 [( ij/rij) 12 Ϫ ( ij/rij) 6 ].…”

Section: Methodsmentioning

confidence: 99%

Dodging the crisis of folding proteins with knots

Sułkowska

Sułkowski

Onuchic

2009

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

168

217

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Proteins with nontrivial topology, containing knots and slipknots, have the ability to fold to their native states without any additional external forces invoked. A mechanism is suggested for folding of these proteins, such as YibK and YbeA, that involves an intermediate configuration with a slipknot. It elucidates the role of topological barriers and backtracking during the folding event. It also illustrates that native contacts are sufficient to guarantee folding in Ϸ1-2% of the simulations, and how slipknot intermediates are needed to reduce the topological bottlenecks. As expected, simulations of proteins with similar structure but with knot removed fold much more efficiently, clearly demonstrating the origin of these topological barriers. Although these studies are based on a simple coarse-grained model, they are already able to extract some of the underlying principles governing folding in such complex topologies. molecular dynamics ͉ slipknots ͉ backtracking ͉ topological barriers D uring the past 2 decades, a joint theoretical and experimental effort has largely advanced the quantitative understanding of the protein folding mechanism. Most small-and intermediate-size proteins live on a minimally frustrated funnel-like energy landscape, which allows fast and robust folding (1-3). Because proteins have been able to solve the energy problem, the final challenge is the structural complexity of the protein folding motifs. Most proteins avoid complex topologies, but recent discoveries have shown that some proteins are actually able to fold into nontrivial topologies where the main chain folds into a knotted conformation (4-6). Although these ''knotted'' folding motifs have been observed, we still have to face the challenging question of how the protein overcomes the kinetic barrier associated with the search of the knotted conformation. We suggest a possible mechanism where the knot formation is preceded by a conformation called a ''slipknot.'' A slipknot is topologically similar to a knot, except that an internal knot is effectively undone as the pathway of the backbone folds back on itself. The fact that such slipknots have already been observed in some protein final structures (7) adds support to this suggestion.This folding mechanism is explored in the context of the two most experimentally investigated knotted families of proteins, Haemophilus influenzae YibK and Escherichia coli YbeA, which are homodimeric ␣/␤-knot methyltransferases (MTases). A schematic representation of these proteins is shown in Fig. 1, [see also supporting information (SI) Fig. S1]. It has been shown experimentally that both these proteins unfold spontaneously and reversibly on addition of chemical denaturant (8-11) and they are able to fold even when additional domains are attached to one or both termini (12). In very recent experimental work (13), based on analysis of the effect of mutations in the knotted region of the protein, a folding model for YibK was also proposed. In this model the threading of the polypeptide chain and fo...

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“…[22][23][24]. Furthermore, there are many Go-model-based proteins for which the supposedly well folding chains are technically bad folders as they have a T f that is smaller or nearly equal to the corresponding value of T g .…”

Section: Introductionmentioning

confidence: 99%

Criteria for folding in structure-based models of proteins

Wołek

Cieplak

2016

The Journal of Chemical Physics

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In structure-based models of proteins, one often assumes that folding is accomplished when all contacts are established. This assumption may frequently lead to a conceptual problem that folding takes place in a temperature region of very low thermodynamic stability, especially when the contact map used is too sparse. We consider six different structure-based models and show that allowing for a small, but model-dependent, percentage of the native contacts not being established boosts the folding temperature substantially while affecting the time scales of folding only in a minor way. We also compare other properties of the six models. We show that the choice of the description of the backbone stiffness has a substantial effect on the values of characteristic temperatures that relate both to equilibrium and kinetic properties. Models without any backbone stiffness (like the self-organized polymer) are found to perform similar to those with the stiffness, including in the studies of stretching.

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Thermal effects in stretching of Go‐like models of titin and secondary structures

Cited by 74 publications

References 46 publications

Thermal unfolding of proteins

Thermal unfolding of proteins

Dodging the crisis of folding proteins with knots

Criteria for folding in structure-based models of proteins

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