The Experts below are selected from a list of 3588 Experts worldwide ranked by ideXlab platform
Herschel Rabitz - One of the best experts on this subject based on the ideXlab platform.
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Macromolecular Crowding Facilitates the Conformational Transition of on-Pathway Molten Globule States of the Prion Protein
The journal of physical chemistry. B, 2016Co-Authors: Fernando Bergasa-caceres, Herschel RabitzAbstract:A simple analytical model is applied to study the effects of Macromolecular Crowding on the stability of partially folded states of the murine prion protein. It is found that relatively low levels of Macromolecular Crowding stabilize the partially folded states. The magnitude of the stabilization effect is similar for the partially folded to that of the fully folded state. Thus, the model suggests that it is on-pathway molten globule-like states, rather than partially folded states arising from unfolding of the native state, that play a key role in the pathogenic interconversion mechanism under crowded conditions.
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Flexibility damps Macromolecular Crowding effects on protein folding dynamics: Application to the murine prion protein (121-231)
Chemical Physics Letters, 2014Co-Authors: Fernando Bergasa-caceres, Herschel RabitzAbstract:Abstract A model of protein folding kinetics is applied to study the combined effects of protein flexibility and Macromolecular Crowding on protein folding rate and stability. It is found that the increase in stability and folding rate promoted by Macromolecular Crowding is damped for proteins with highly flexible native structures. The model is applied to the folding dynamics of the murine prion protein (121–231). It is found that the high flexibility of the native isoform of the murine prion protein (121–231) reduces the effects of Macromolecular Crowding on its folding dynamics. The relevance of these findings for the pathogenic mechanism are discussed.
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A simple quantitative model of Macromolecular Crowding effects on protein folding: Application to the murine prion protein(121–231)
Chemical Physics Letters, 2013Co-Authors: Fernando Bergasa-caceres, Herschel RabitzAbstract:Abstract A model of protein folding kinetics is applied to study the effects of Macromolecular Crowding on protein folding rate and stability. Macromolecular Crowding is found to promote a decrease of the entropic cost of folding of proteins that produces an increase of both the stability and the folding rate. The acceleration of the folding rate due to Macromolecular Crowding is shown to be a topology-dependent effect. The model is applied to the folding dynamics of the murine prion protein (121–231). The differential effect of Macromolecular Crowding as a function of protein topology suffices to make non-native configurations relatively more accessible.
Fernando Bergasa-caceres - One of the best experts on this subject based on the ideXlab platform.
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Macromolecular Crowding Facilitates the Conformational Transition of on-Pathway Molten Globule States of the Prion Protein
The journal of physical chemistry. B, 2016Co-Authors: Fernando Bergasa-caceres, Herschel RabitzAbstract:A simple analytical model is applied to study the effects of Macromolecular Crowding on the stability of partially folded states of the murine prion protein. It is found that relatively low levels of Macromolecular Crowding stabilize the partially folded states. The magnitude of the stabilization effect is similar for the partially folded to that of the fully folded state. Thus, the model suggests that it is on-pathway molten globule-like states, rather than partially folded states arising from unfolding of the native state, that play a key role in the pathogenic interconversion mechanism under crowded conditions.
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Flexibility damps Macromolecular Crowding effects on protein folding dynamics: Application to the murine prion protein (121-231)
Chemical Physics Letters, 2014Co-Authors: Fernando Bergasa-caceres, Herschel RabitzAbstract:Abstract A model of protein folding kinetics is applied to study the combined effects of protein flexibility and Macromolecular Crowding on protein folding rate and stability. It is found that the increase in stability and folding rate promoted by Macromolecular Crowding is damped for proteins with highly flexible native structures. The model is applied to the folding dynamics of the murine prion protein (121–231). It is found that the high flexibility of the native isoform of the murine prion protein (121–231) reduces the effects of Macromolecular Crowding on its folding dynamics. The relevance of these findings for the pathogenic mechanism are discussed.
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A simple quantitative model of Macromolecular Crowding effects on protein folding: Application to the murine prion protein(121–231)
Chemical Physics Letters, 2013Co-Authors: Fernando Bergasa-caceres, Herschel RabitzAbstract:Abstract A model of protein folding kinetics is applied to study the effects of Macromolecular Crowding on protein folding rate and stability. Macromolecular Crowding is found to promote a decrease of the entropic cost of folding of proteins that produces an increase of both the stability and the folding rate. The acceleration of the folding rate due to Macromolecular Crowding is shown to be a topology-dependent effect. The model is applied to the folding dynamics of the murine prion protein (121–231). The differential effect of Macromolecular Crowding as a function of protein topology suffices to make non-native configurations relatively more accessible.
S Longeville - One of the best experts on this subject based on the ideXlab platform.
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Compression of random coils due to Macromolecular Crowding: scaling effects.
Physical Review E, 2010Co-Authors: C Le Coeur, J Teixeira, P Busch, S LongevilleAbstract:The addition of a Macromolecular Crowding agent to a dilute solution of polymer exerts a compressive force that tends to reduce the size of the chain. We study here the effect of changing the size ratio between the random coil and the Crowding agent. The compression occurs at lower Crowding agent concentration, $\ensuremath{\Phi}$ when polymer molecular weight increases. The Flory exponent $\ensuremath{\nu}(\ensuremath{\Phi})$ decreases from $\ensuremath{\nu}(0)\ensuremath{\simeq}0.48$ in water down to 0.3 with Macromolecular Crowding. The effective polymer-polymer interactions change from repulsive to strongly attractive inducing aggregation of the chains. This effect changes drastically for larger polymer sizes, being much more pronounced at high molecular weights.
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Compression of random coils due to Macromolecular Crowding: scaling effects.
Physical review. E Statistical nonlinear and soft matter physics, 2010Co-Authors: C Le Coeur, J Teixeira, P Busch, S LongevilleAbstract:The addition of a Macromolecular Crowding agent to a dilute solution of polymer exerts a compressive force that tends to reduce the size of the chain. We study here the effect of changing the size ratio between the random coil and the Crowding agent. The compression occurs at lower Crowding agent concentration, Φ when polymer molecular weight increases. The Flory exponent ν(Φ) decreases from ν(0)≃0.48 in water down to 0.3 with Macromolecular Crowding. The effective polymer-polymer interactions change from repulsive to strongly attractive inducing aggregation of the chains. This effect changes drastically for larger polymer sizes, being much more pronounced at high molecular weights.
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Compression of random coils due to Macromolecular Crowding.
Physical review. E Statistical nonlinear and soft matter physics, 2009Co-Authors: C Le Coeur, B Demé, S LongevilleAbstract:The conformation of a linear polymer chain is studied as a function of the concentration of a Macromolecular Crowding agent by neutron scattering. Excluded volume to random coil due to Macromolecular Crowding in cells is predicted to exert a compressive force that will tend to reduce its size. It is shown that when reducing free volume due to Macromolecular Crowding, we observe a compression of the polymer chain with a reduction in its radius of gyration of up to approximately 30% and that the effective chain-chain interactions are strongly modified.
Vladimir N. Uversky - One of the best experts on this subject based on the ideXlab platform.
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What Macromolecular Crowding Can Do to a Protein
International journal of molecular sciences, 2014Co-Authors: Irina M. Kuznetsova, Konstantin K. Turoverov, Vladimir N. UverskyAbstract:The intracellular environment represents an extremely crowded milieu, with a limited amount of free water and an almost complete lack of unoccupied space. Obviously, slightly salted aqueous solutions containing low concentrations of a biomolecule of interest are too simplistic to mimic the “real life” situation, where the biomolecule of interest scrambles and wades through the tightly packed crowd. In laboratory practice, such Macromolecular Crowding is typically mimicked by concentrated solutions of various polymers that serve as model “Crowding agents”. Studies under these conditions revealed that Macromolecular Crowding might affect protein structure, folding, shape, conformational stability, binding of small molecules, enzymatic activity, protein-protein interactions, protein-nucleic acid interactions, and pathological aggregation. The goal of this review is to systematically analyze currently available experimental data on the variety of effects of Macromolecular Crowding on a protein molecule. The review covers more than 320 papers and therefore represents one of the most comprehensive compendia of the current knowledge in this exciting area.
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Guiding protein aggregation with Macromolecular Crowding.
Biochemistry, 2008Co-Authors: Larissa A. Munishkina, Atta Ahmad, Anthony L. Fink, Vladimir N. UverskyAbstract:Macromolecular Crowding is expected to have a significant effect on protein aggregation. In the present study we analyzed the effect of Macromolecular Crowding on fibrillation of four proteins, bovine S-carboxymethyl-alpha-lactalbumin (a disordered form of the protein with reduced three out of four disulfide bridges), human insulin, bovine core histones, and human alpha-synuclein. These proteins are structurally different, varying from natively unfolded (alpha-synuclein and core histones) to folded proteins with rigid tertiary and quaternary structures (monomeric and hexameric forms of insulin). All these proteins are known to fibrillate in diluted solutions, however their aggregation mechanisms are very divers and some of them are able to form different aggregates in addition to fibrils. We studied how Macromolecular Crowding guides protein between different aggregation pathways by analyzing the effect of Crowding agents on the aggregation patterns under the variety of conditions favoring different aggregated end products in diluted solutions.
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The effect of Macromolecular Crowding on protein aggregation and amyloid fibril formation.
Journal of molecular recognition : JMR, 2004Co-Authors: Larissa A. Munishkina, Vladimir N. Uversky, Elisa M. Cooper, Anthony L. FinkAbstract:Macromolecular Crowding is expected to have several significant effects on protein aggregation; the major effects will be those due to excluded volume and increased viscosity. In this report we summarize data demonstrating that Macromolecular Crowding may lead to a dramatic acceleration in the rate of protein aggregation and formation of amyloid fibrils, using the protein α-synuclein. The aggregation of α-synuclein has been implicated as a critical factor in development of Parkinson's disease. Various types of polymers, from neutral polyethylene glycols and polysaccharides (Ficolls, dextrans) to inert proteins, are shown to accelerate α-synuclein fibrillation. The stimulation of fibrillation increases with increasing length of polymer, as well as increasing polymer concentration. At lower polymer concentrations (typically up to ∼100 mg/ml) the major effect is ascribed to excluded volume, whereas at higher polymer concentrations evidence of opposing viscosity effects become apparent. Pesticides and metals, which are linked to increased risk of Parkinson's disease by epidemiological studies, are shown to accelerate α-synuclein fibrillation under conditions of molecular Crowding. Copyright © 2004 John Wiley & Sons, Ltd.
Jeetain Mittal - One of the best experts on this subject based on the ideXlab platform.
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Macromolecular Crowding effects on protein–protein binding affinity and specificity
The Journal of chemical physics, 2010Co-Authors: Young C. Kim, Robert B. Best, Jeetain MittalAbstract:Macromolecular Crowding in cells is recognized to have a significant impact on biological function, yet quantitative models for its effects are relatively undeveloped. The influence of Crowding on protein–protein interactions is of particular interest, since these mediate many processes in the cell, including the self-assembly of larger complexes, recognition, and signaling. We use a residue-level coarse-grained model to investigate the effects of Macromolecular Crowding on the assembly of protein–protein complexes. Interactions between the proteins are treated using a fully transferable energy function, and interactions of protein residues with the spherical crowders are repulsive. We show that the binding free energy for two protein complexes, ubiquitin/UIM1 and cytochrome c/cytochrome c peroxidase, decreases modestly as the concentration of Crowding agents increases. To obtain a quantitative description of the stabilizing effect, we map the aspherical individual proteins and protein complexes onto sphe...
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Macromolecular Crowding effects on protein protein binding affinity and specificity
Journal of Chemical Physics, 2010Co-Authors: Young C. Kim, Robert B. Best, Jeetain MittalAbstract:Macromolecular Crowding in cells is recognized to have a significant impact on biological function, yet quantitative models for its effects are relatively undeveloped. The influence of Crowding on protein–protein interactions is of particular interest, since these mediate many processes in the cell, including the self-assembly of larger complexes, recognition, and signaling. We use a residue-level coarse-grained model to investigate the effects of Macromolecular Crowding on the assembly of protein–protein complexes. Interactions between the proteins are treated using a fully transferable energy function, and interactions of protein residues with the spherical crowders are repulsive. We show that the binding free energy for two protein complexes, ubiquitin/UIM1 and cytochrome c/cytochrome c peroxidase, decreases modestly as the concentration of Crowding agents increases. To obtain a quantitative description of the stabilizing effect, we map the aspherical individual proteins and protein complexes onto sphe...
