In Silico Evidence That Protein Unfolding is a Precursor of Protein Aggregation

Bianco, Valentino; Franzese, Giancarlo; Coluzza, Ivan

doi:10.1002/cphc.201900904

Cited by 22 publications

(40 citation statements)

References 83 publications

(195 reference statements)

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“…To tackle computationally the folding/aggregation problem in solutions involving tens of proteins we adopt a coarse-grain model for protein solvated by water, [23][24][25][26][27][28][29] based on a wa-ter model that reproduces-at least qualitatively-the thermodynamic properties of the sol-vent. [30][31][32] We perform Monte Carlo simulations to design artificial protein structures, with a well tested scheme, 33,34 recently extended to optimize the protein sequence to the water properties at a given temperature and pressure.…”

Section: Resultsmentioning

confidence: 99%

“…when solvated in heterogeneous solutions (multiple copies of different proteins) compared 4 to their aggregation concentration (determined in our previous study23 ) in homogeneous solutions (multiple copies of the same protein). Finally, we have verified these conclusions experimentally by the evaluation of the aggregation behaviour of two model proteins, the bovine serum albumin (BSA) and the consensus tetratricopeptide repeat (CTPR).…”

mentioning

confidence: 98%

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Proteins are Solitary! Pathways of Protein Folding and Aggregation in Protein Mixtures

Bianco

Alonso‐Navarro

Silvio

et al. 2019

J. Phys. Chem. Lett.

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We present a computational and experimental study on the folding and aggregation in solutions of multiple protein mixtures at different concentrations. We show how in protein mixtures, each component is capable of maintaining its folded state at desensitises higher then the one at which they would precipitate in single species solutions. We demonstrate the generality of our observation over many different proteins using computer simulations capable of fully characterising the cross-aggregation phase diagram of all the mixtures. Dynamic light Scattering experiments were performed to evaluate the aggregation of two proteins, the bovine serum albumin (BSA) and the consensus tetratricopeptide repeat (CTPR), in solutions of one or both proteins. The experiment confirm our hypothesis and the simulations. These findings elucidate critical aspects on the cross-regulation of expression and aggregation of proteins exerted by the cell and on the evolutionary selection of folding and not-aggregating protein sequences, paving the way for new experimental tests.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 98%

Proteins are Solitary! Pathways of Protein Folding and Aggregation in Protein Mixtures

Bianco

Alonso‐Navarro

Silvio

et al. 2019

J. Phys. Chem. Lett.

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“…The amino acids interact through the nearest neighbor potential given by the Miyazawa-Jerningan interaction matrix [49]. To account for the lower surface-volume ratio in 2D, we scale the matrix by a factor of 2, increasing the effective amino acids interactions [30].…”

Section: Protein and Interface Modelmentioning

confidence: 99%

“…For example, a recent study showed that the concentration increase of individual protein species can unfold their native state without inducing their aggregation [30]. Furthermore, each component in a protein mixture can keep its folded state at densities that are larger than those at which they would precipitate if they were in a single-specie solution [31].…”

Section: Introductionmentioning

confidence: 99%

“…Here, following the approach in Ref. [30,31], we present a computational study on the protein folding/unfolding and aggregation near a hydrophobic interface, representative of a portion of a nanomaterial. By performing Monte Carlo simulations, we describe the formation of aggregates against folded conformations at different temperatures, both in the bulk water and at the hydrophobic interface.…”

Section: Introductionmentioning

confidence: 99%

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Protein Unfolding and Aggregation near a Hydrophobic Interface

March,

Bianco,

Franzese

2021

Preprint

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The behavior of proteins near interfaces is relevant for biological and medical purposes. Previous results in bulk show that, when the protein concentration increases, the proteins unfold and, at higher concentrations, aggregate. Here, we study how the presence of a hydrophobic surface affects this course of events. To this goal, we use a coarse-grained model of proteins and study by simulations their folding and aggregation near an ideal hydrophobic surface in an aqueous environment by changing parameters such as temperature and hydrophobic strength, related, e.g., to ions concentration. We show that the hydrophobic surface, as well as the other parameters, affect both the protein unfolding and aggregation. We discuss the interpretation of these results and define future lines for further analysis, with their possible implications in neurodegenerative diseases.

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Water Contribution to the Protein Folding and Its Relevance in Protein Design and Protein Aggregation

Franzese

Rojas

Bianco

et al. 2021

Springer Proceedings in Physics

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Water plays a fundamental role in protein stability. However, the effect of the properties of water on the behaviour of proteins is only partially understood. Several theories have been proposed to give insight into the mechanisms of cold and pressure denaturation, or the limits of temperature and pressure above which no protein has a stable, functional state, or how unfolding and aggregation are related. Here we review our results based on a theoretical approach that can rationalise the water contribution to protein solutions' free energy. We show, using Monte Carlo simulations, how we can rationalise experimental data with our recent results. We discuss how our findings can help develop new strategies for the design of novel synthetic biopolymers or possible approaches for mitigating neurodegenerative pathologies.

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In Silico Evidence That Protein Unfolding is a Precursor of Protein Aggregation

Cited by 22 publications

References 83 publications

Proteins are Solitary! Pathways of Protein Folding and Aggregation in Protein Mixtures

Proteins are Solitary! Pathways of Protein Folding and Aggregation in Protein Mixtures

Protein Unfolding and Aggregation near a Hydrophobic Interface

Water Contribution to the Protein Folding and Its Relevance in Protein Design and Protein Aggregation

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