Thermodynamics of Aggregation of Two Proteins

Nakanishi, Kazuki; Kikuchi, Macoto

doi:10.1143/jpsj.75.064803

Cited by 5 publications

(3 citation statements)

References 15 publications

(19 reference statements)

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“…As L decreases, the thermal stability of the complexes increases because of the decrease in the translational entropy of the free states. This result suggests that confinement in a small volume can also induce binding, which is basically the same as the confinement-induced dimerization discussed by Nakanishi and Kikuchi 34 . Increasing the density of the two molecules can also reduce translational entropy of the free states, and stabilize bound states.…”

Section: B Thermal Stability Of the Native Bound Statesupporting

confidence: 79%

“…We calculated the number of states by using the multiself-overlap ensemble (MSOE) Monte Carlo method 30,31 , which is an extended version of the multicanonical Monte Carlo method 32,33 . The MSOE is a powerful tool in analyzing thermal properties of lattice polymers 28,34 , and is applied for statistical enumeration of self-avoiding walks 35 . The MSOE successfully attained thermal equilibrium between free states and the designed bound state.…”

Section: Model and Methodsmentioning

confidence: 99%

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Structural flexibility of intrinsically disordered proteins induces stepwise target recognition

Shirai

Kikuchi

2013

The Journal of Chemical Physics

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An intrinsically disordered protein (IDP) lacks a stable three-dimensional structure, while it folds into a specific structure when it binds to a target molecule. In some IDP-target complexes, not all target binding surfaces are exposed on the outside, and intermediate states are observed in their binding processes. We consider that stepwise target recognition via intermediate states is a characteristic of IDP binding to targets with "hidden" binding sites. To investigate IDP binding to hidden target binding sites, we constructed an IDP lattice model based on the HP model. In our model, the IDP is modeled as a chain and the target is modeled as a highly coarse-grained object. We introduced motion and internal interactions to the target to hide its binding sites. In the case of unhidden binding sites, a two-state transition between the free states and a bound state is observed, and we consider that this represents coupled folding and binding. Introducing hidden binding sites, we found an intermediate bound state in which the IDP forms various structures to temporarily stabilize the complex. The intermediate state provides a scaffold for the IDP to access the hidden binding site. We call this process multiform binding. We conclude that structural flexibility of IDPs enables them to access hidden binding sites and this is a functional advantage of IDPs.

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Section: B Thermal Stability Of the Native Bound Statesupporting

confidence: 79%

Section: Model and Methodsmentioning

confidence: 99%

Structural flexibility of intrinsically disordered proteins induces stepwise target recognition

Shirai

Kikuchi

2013

The Journal of Chemical Physics

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“…When systems comprising up to 40 chains were simulated, some of these conformations were prone to aggregation. Recently, Nakanishi and Kikuchi [136] performed a rigorous thermodynamic analysis on the aggregation of two HP proteins. To overcome problems with the excluded volume, they used multi-self-overlap-ensemble Monte Carlo, which allows chains to move through each other.…”

Section: Lattice Studies Of Aggregationmentioning

confidence: 99%

Search Strategies in Structural Bioinformatics

Oakley

Barthel²,

Bykov³

et al. 2008

CPPS

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Optimisation problems pervade structural bioinformatics. In this review, we describe recent work addressing a selection of bioinformatics challenges. We begin with a discussion of research into protein structure comparison, and highlight the utility of Kolmogorov complexity as a measure of structural similarity. We then turn to research into de novo protein structure prediction, in which structures are generated from first principles. In this endeavour, there is a compromise between the detail of the model and the extent to which the conformational space of the protein can be sampled. We discuss some developments in this area, including off-lattice structure prediction using the great deluge algorithm. One strategy to reduce the size of the search space is to restrict the protein chain to sites on a regular lattice. In this context, we highlight the use of memetic algorithms, which combine genetic algorithms with local optimisation, to the study of simple protein models on the two-dimensional square lattice and the face-centred cubic lattice.

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Study of the aggregation mechanism of polyglutamine peptides using replica exchange molecular dynamics simulations

2013

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Polyglutamine (polyQ, a peptide) with an abnormal repeat length is the causative agent of polyQ diseases, such as Huntington's disease. Although glutamine is a polar residue, polyQ peptides form insoluble aggregates in water, and the mechanism for this aggregation is still unclear. To elucidate the detailed mechanism for the nucleation and aggregation of polyQ peptides, replica exchange molecular dynamics simulations were performed for monomers and dimers of polyQ peptides with several chain lengths. Furthermore, to determine how the aggregation mechanism of polyQ differs from those of other peptides, we compared the results for polyQ with those of polyasparagine and polyleucine. The energy barrier between the monomeric and dimeric states of polyQ was found to be relatively low, and it was observed that polyQ dimers strongly favor the formation of antiparallel β-sheet structures. We also found a characteristic behavior of the monomeric polyQ peptide: a turn at the eighth residue is always present, even when the chain length is varied. We previously showed that a structure including more than two sets of β-turns is stable, so a long monomeric polyQ chain can act as an aggregation nucleus by forming several pairs of antiparallel β-sheet structures within a single chain. Since the aggregation of polyQ peptides has some features in common with an amyloid fibril, our results shed light on the mechanism for the aggregation of polyQ peptides as well as the mechanism for the formation of general amyloid fibrils, which cause the onset of amyloid diseases.

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Thermodynamics of Aggregation of Two Proteins

Cited by 5 publications

References 15 publications

Structural flexibility of intrinsically disordered proteins induces stepwise target recognition

Structural flexibility of intrinsically disordered proteins induces stepwise target recognition

Search Strategies in Structural Bioinformatics

Study of the aggregation mechanism of polyglutamine peptides using replica exchange molecular dynamics simulations

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