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FRANCESCO TAVANTI

DIPENDENTE ALTRO ENTE DI RICERCA
Dipartimento di Scienze Fisiche, Informatiche e Matematiche sede ex-Fisica

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Pubblicazioni

2023 - A HydroDynamic Model for Trap-Assisted Tunneling Conduction in Ovonic Devices [Articolo su rivista]
Buscemi, F; Piccinini, E; Vandelli, L; Nardi, F; Padovani, A; Kaczer, B; Garbin, D; Clima, S; Degraeve, R; Kar, Gs; Tavanti, F; Slassi, A; Calzolari, A; Larcher, L
abstract

Electrical conduction in ovonic threshold switching (OTS) devices is described by introducing a new physical model where the multiphonon trap-assisted tun-neling (TAT) is coupled to a hydrodynamic theory. Static and transient electrical responses from Ge(x)Se(1-x )experimental devices are reproduced, outlining the role played by the material properties like mobility gap and defects in tuning the OTS performances. A clear physical interpretation of the mechanisms ruling the different OTS conduction regimes (off, threshold, on) is presented. A nanoscopic picture of the processes featuring the carrier transport is also given. The impact of geometry, temperature, and material mod-ifications on device performance is discussed providing physical insight into the optimization of OTS devices.

2023 - Device‐to‐Materials Pathway for Electron Traps Detection in Amorphous GeSe‐Based Selectors [Articolo su rivista]
Slassi, Amine; Medondjio, Linda‐sheila; Padovani, Andrea; Tavanti, Francesco; He, Xu; Clima, Sergiu; Garbin, Daniele; Kaczer, Ben; Larcher, Luca; Ordejón, Pablo; Calzolari, Arrigo
abstract

The choice of the ideal material employed in selector devices is a tough task both from the theoretical and experimental side, especially due to the lack of a synergistic approach between techniques able to correlate specific material properties with device characteristics. Using a material-to-device multiscale technique, we propose a reliable protocol for an efficient characterization of the active traps in amorphous GeSe chalcogenide. The resulting trap maps trace back the specific features of materials responsible for the measured findings, and connect them to an atomistic description of the sample. Our metrological approach can be straightforwardly extended to other materials and devices, which is very beneficial for an efficient material-device co-design and the optimization of novel technologies.

2022 - BELLO: A post-processing tool for the local-order analysis of disordered systems [Articolo su rivista]
Dianat, B.; Tavanti, F.; Padovani, A.; Larcher, L.; Calzolari, A.
abstract

The characterization of the atomic structure of disordered systems, such as amorphous, glasses and (bio)molecule in solution, is a fundamental step for most theoretical investigations. The properties of short- and medium-range local order structures are responsible for the electronic, optical and transport properties of these systems. Here, we present the BELLO open source code, a post-processing script-tool created for the automatic analysis and extraction of structural characteristics of disordered and amorphous systems. BELLO is agnostic to the code that generated single configurations or trajectories, it provides an intuitive access through a graphical user interface (GUI), and it requires minimal computational resources. Its capabilities include the calculation of the order parameter q, the folded structure identification, and statistical analysis tools such as atomic coordination number and pair/angle-distribution functions. The working principles of the code are described and tested on ab initio molecular dynamics trajectories of amorphous chalcogenides.

2022 - Structure Analysis and Properties Calculations [Capitolo/Saggio]
Presti, D.; Muniz-Miranda, F.; Tavanti, F.; Pedone, A.
abstract

2021 - Disclosing the interaction of gold nanoparticles with aβ(1–40) monomers through replica exchange molecular dynamics simulations [Articolo su rivista]
Tavanti, F.; Pedone, A.; Menziani, M. C.
abstract

Amyloid-β aggregation is one of the principal causes of amyloidogenic diseases that lead to the loss of neuronal cells and to cognitive impairments. The use of gold nanoparticles treating amyloidogenic diseases is a promising approach, because the chemistry of the gold surface can be tuned in order to have a specific binding, obtaining effective tools to control the aggregation. In this paper, we show, by means of Replica Exchange Solute Tempering Molecular Simulations, how electrostatic interactions drive the absorption of Amyloid-β monomers onto citrates-capped gold nanoparticles. Importantly, upon binding, amyloid monomers show a reduced propensity in forming β-sheets secondary structures that are characteristics of mature amyloid fibrils.

2021 - Exploring the crystallization path of lithium disilicate through metadynamics simulations [Articolo su rivista]
Lodesani, F.; Tavanti, F.; Menziani, M. C.; Maeda, K.; Takato, Y.; Urata, S.; Pedone, A.
abstract

Understanding the crystallization mechanism in silica-based materials is of paramount importance to comprehend geological phenomena and to design novel materials for a variety of technological and industrial applications. In this work, we show that metadynamics simulations can effectively overcome a large energy barrier to crystallize from viscous oxide glass melts and can be used to identify the melt-to-crystal transition path of the lithium disilicate system. The accelerated atomistic simulation revealed of a two-step mechanism of the nanoscale crystal formation. First, a partially layered silica embryo appeared, and then a more ordered crystalline layer with size larger than the critical nucleus size was formed. Subsequently, lithium ions piled up around the silicate layer and triggered stacking of adjacent silicate layers, which eventually built a perfect crystal. Contrarily to previous hypotheses, no lithium metasilicate crystal was observed as a precursor of the homogeneous crystallization of lithium disilicate.

2020 - Computational insights into the binding of monolayer-capped gold nanoparticles onto amyloid-β fibrils [Articolo su rivista]
Tavanti, F.; Pedone, A.; Menziani, M. C.; Alexander-Katz, A.
abstract

Amyloids-β (Aβ) fibrils are involved in several neurodegenerative diseases. In this study, atomistic molecular dynamics simulations have been used to investigate how monolayer-protected gold nanoparticles interact with Aβ(1-40) and Aβ(1-42) fibrils. Our results show that small gold nanoparticles bind with the external side of amyloid-β fibrils that is involved in the fibrillation process. The binding affinity, studied for both kinds of fibrils as a function of the monolayer composition and the nanoparticle diameter, is modulated by hydrophobic interactions and ligand monolayer conformation. Our findings thus show that monolayer-protected nanoparticles are good candidates to prevent fibril aggregation and secondary nucleation or to deliver drugs to specific fibril regions.

2020 - Insights into the effect of curcumin and (–)-epigallocatechin-3-gallate on the aggregation of aβ(1–40) monomers by means of molecular dynamics [Articolo su rivista]
Tavanti, F.; Pedone, A.; Menziani, M. C.
abstract

In this study, we compared the effects of two well-known natural compounds on the early step of the fibrillation process of amyloid-β (1–40), responsible for the formation of plaques in the brains of patients affected by Alzheimer’s disease (AD). The use of extensive replica exchange simulations up to the µs scale allowed us to characterize the inhibition activity of (–)-epigallocatechin-3-gallate (EGCG) and curcumin (CUR) on unfolded amyloid fibrils. A reduced number of β-strands, characteristic of amyloid fibrils, and an increased distance between the amino acids that are responsible for the intra-and interprotein aggregations are observed. The central core region of the amyloid-β (Aβ(1–40)) fibril is found to have a high affinity to EGCG and CUR due to the presence of hydrophobic residues. Lastly, the free binding energy computed using the Poisson Boltzmann Surface Ares suggests that EGCG is more likely to bind to unfolded Aβ(1–40) fibrils and that this molecule can be a good candidate to develop new and more effective congeners to treat AD.

2020 - Unraveling the complexity of amyloid polymorphism using gold nanoparticles and cryo-EM [Articolo su rivista]
Cendrowska, U.; Silva, P. J.; Ait-Bouziad, N.; Muller, M.; Guven, Z. P.; Vieweg, S.; Chiki, A.; Radamaker, L.; Kumar, S. T.; Fandrich, M.; Tavanti, F.; Menziani, M. C.; Alexander-Katz, A.; Stellacci, F.; Lashuel, H. A.
abstract

Increasing evidence suggests that amyloid polymorphism gives rise to different strains of amyloids with distinct toxicities and pathology-spreading properties. Validating this hypothesis is challenging due to a lack of tools and methods that allow for the direct characterization of amyloid polymorphism in hydrated and complex biological samples. Here, we report on the development of 11-mercapto-1-undecanesulfonate-coated gold nanoparticles (NPs) that efficiently label the edges of synthetic, recombinant, and native amyloid fibrils derived from different amyloidogenic proteins. We demonstrate that these NPs represent powerful tools for assessing amyloid morphological polymorphism, using cryogenic transmission electron microscopy (cryo-EM). The NPs allowed for the visualization of morphological features that are not directly observed using standard imaging techniques, including transmission electron microscopy with use of the negative stain or cryo-EM imaging. The use of these NPs to label native paired helical filaments (PHFs) from the postmortem brain of a patient with Alzheimer's disease, as well as amyloid fibrils extracted from the heart tissue of a patient suffering from systemic amyloid light-chain amyloidosis, revealed a high degree of homogeneity across the fibrils derived from human tissue in comparison with fibrils aggregated in vitro. These findings are consistent with, and strongly support, the emerging view that the physiologic milieu is a key determinant of amyloid fibril strains. Together, these advances should not only facilitate the profiling and characterization of amyloids for structural studies by cryo-EM, but also pave the way to elucidate the structural basis of amyloid strains and toxicity, and possibly the correlation between the pathological and clinical heterogeneity of amyloid diseases.

2019 - DARPin_9-29-Targeted Mini Gold Nanorods Specifically Eliminate HER2-Overexpressing Cancer Cells [Articolo su rivista]
Proshkina G., Deyev S.; A., Ryabova; Tavanti, Francesco; Menziani, Maria Cristina; R., Cohen; L., Katrivas; A., Kotlyar
abstract

We have demonstrated that designed ankyrin repeat protein (DARPin)_9-29, which specifically targets human epidermal growth factor receptor 2 (HER2), binds tightly to gold mini nanorods (GNRs). Molecular dynamic simulations showed that a single layer of DARPin_9-29 molecules is formed on the surface of the nanorod and that conjugation with the nanorod does not involve the protein's domain responsible for specific binding to HER2. The nanorod-DARPin (DARPin-GNR) conjugate is specifically bound (in nanomolar concentrations) to human breast adenocarcinoma SK-BR-3 cells overexpressing HER2. Illumination by near-infrared light (850 nm) led to almost complete eradication of the conjugate-treated SK-BR-3 cells; the viability of epithelial human breast cancer cells expressing normal amounts of the receptor was much less affected by the illumination. The results reported here pave the way toward application of DARPin-GNR conjugates in phototherapy of cancer.

2019 - Functionalization of protein hexahistidine tags by functional nanoreactors [Articolo su rivista]
Paolino, M.; Visintin, M.; Margotti, E.; Visentini, M.; Salvini, L.; Reale, A.; Razzano, V.; Giuliani, G.; Caselli, G.; Tavanti, F.; Menziani, Maria Cristina; Cappelli, A.
abstract

A water-soluble Morita-Baylis-Hillman adduct (MBHA) derivative (3) was previously shown to self-assemble in a water environment into functional nanoreactors capable of performing multiple attacks and functionalization of N-acetylhexahistidine. In order to challenge this intriguing reactivity in a model protein more complex than N-acetylhexahistidine, the single-chain Fv antibody CRB0137 was characterized from the point of view of its structure and made to react with 3 in kinetics experiments. The results of these studies suggested that MBHA derivative 3 reacted typically with the amino acid residues of the CRB0137 hexahistidine tag leading to the formation of multi-PEGylated species. Overall, they demonstrate the viability of a new methodology for the site-specific PEGylation of engineered proteins bearing poly-histidine tags.

2019 - Multiscale Molecular Dynamics Simulation of Multiple Protein Adsorption on Gold Nanoparticles [Articolo su rivista]
Tavanti, F.; Pedone, A.; Menziani, M. C.
abstract

A multiscale molecular dynamics simulation study has been carried out in order to provide in-depth information on the adsorption of hemoglobin, myoglobin, and trypsin over citrate-capped AuNPs of 15 nm diameter. In particular, determinants for single proteins adsorption and simultaneous adsorption of the three types of proteins considered have been studied by Coarse-Grained and Meso-Scale molecular simulations, respectively. The results, discussed in the light of the controversial experimental data reported in the current experimental literature, have provided a detailed description of the (i) recognition process, (ii) number of proteins involved in the early stages of corona formation, (iii) protein competition for AuNP adsorption, (iv) interaction modalities between AuNP and protein binding sites, and (v) protein structural preservation and alteration.

2019 - Nanoreactors for the multi-functionalization of poly-histidine fragments [Articolo su rivista]
Paolino, M.; Reale, A.; Razzano, V.; Giuliani, G.; Donati, A.; Bonechi, C.; Caselli, G.; Visintin, M.; Makovec, F.; Scialabba, C.; Licciardi, M.; Paccagnini, E.; Gentile, M.; Salvini, L.; Tavanti, F.; Menziani, M. C.; Cappelli, A.
abstract

Water-soluble MBHA derivatives were found to self-assemble in a water environment to generate aggregates showing core-shell architectures. The aggregates appeared to be capable of working as nanoreactors performing a multi-functionalization of poly-histidine fragments, which after an initial interaction with the solvated oligo(ethylene glycol) shell reach the reactive core.

2018 - An atomic-level look at the structure-property relationship of cerium-doped glasses using classical molecular dynamics [Articolo su rivista]
Pedone, Alfonso; Tavanti, Francesco; Malavasi, Gianluca; Menziani, Maria Cristina
abstract

Ce-containing bioactive glasses are of great interest in biomedical field since they exert antioxidant properties associated with low toxicity and a broad spectrum of bacteriostatic activities. The results obtained by classical molecular dynamics simulations allow the elucidation of the correlations between the effect of the inclusion of cerium doping ions into the structure of phosphosilicate and silicate bioactive glasses and their properties. The addition of small quantities of Ce to the silicate bioglass favours the depolymerisation of the silicate network with a positive effect on the ability to dissolve in body fluid. Moreover, the under coordination of both the Ce3+ and Ce4+ species in these glasses enhances their catalytic activity towards hydrogen peroxide. Conversely, the formation of cerium phosphate domains in the phosphosilicate glasses leads to detrimental effects for both the solubility and the catalytic activity of the glasses. Finally, a new quantitative view of the structure-activity relationships governing the macroscopic properties of these glasses has been obtained by means of structural descriptor that takes into account the fragmentation of the Si network and the consequent rearrangement of the modifier ions and the network destruction per cerium unit descriptor.

2018 - Computational Insight into the Effect of Natural Compounds on the Destabilization of Preformed Amyloid-β(1⁻40) Fibrils [Articolo su rivista]
Tavanti, Francesco; Pedone, Alfonso; Menziani, Maria Cristina
abstract

One of the principal hallmarks of Alzheimer's disease (AD) is related to the aggregation of amyloid-β fibrils in an insoluble form in the brain, also known as amyloidosis. Therefore, a prominent therapeutic strategy against AD consists of either blocking the amyloid aggregation and/or destroying the already formed aggregates. Natural products have shown significant therapeutic potential as amyloid inhibitors from in vitro studies as well as in vivo animal tests. In this study, the interaction of five natural biophenols (curcumin, dopamine, (-)-epigallocatechin-3-gallate, quercetin, and rosmarinic acid) with amyloid-β(1⁻40) fibrils has been studied through computational simulations. The results allowed the identification and characterization of the different binding modalities of each compounds and their consequences on fibril dynamics and aggregation. It emerges that the lateral aggregation of the fibrils is strongly influenced by the intercalation of the ligands, which modulates the double-layered structure stability.

2018 - Curcumin derivatives and Aβ-fibrillar aggregates: An interactions’ study for diagnostic/therapeutic purposes in neurodegenerative diseases [Articolo su rivista]
Orteca, Giulia; Tavanti, Francesco; Bednarikova, Zuzana; Gazova, Zuzana; Rigillo, Giovanna; Imbriano, Carol; Basile, Valentina; Asti, Mattia; Rigamonti, Luca; Saladini, Monica; Ferrari, Erika; Menziani, Maria Cristina
abstract

Several neurodegenerative diseases, like Alzheimer's (AD), are characterized by amyloid fibrillar deposition of misfolded proteins, and this feature can be exploited for both diagnosis and therapy design. In this paper, structural modifications of curcumin scaffold were examined in order to improve its bioavailability and stability in physiological conditions, as well as its ability to interfere with β-amyloid fibrils and aggregates. The acid-base behaviour of curcumin derivatives, their pharmacokinetic stability in physiological conditions, and in vitro ability to interfere with Aβ fibrils at different incubation time were investigated. The mechanisms governing these phenomena have been studied at atomic level by means of molecular docking and dynamic simulations. Finally, biological activity of selected curcuminoids has been investigated in vitro to evaluate their safety and efficiency in oxidative stress protection on hippocampal HT-22 mouse cells. Two aromatic rings, π-conjugated structure and H-donor/acceptor substituents on the aromatic rings showed to be the sine qua non structural features to provide interaction and disaggregation activity even at very low incubation time (2h). Computational simulations proved that upon binding the ligands modify the conformational dynamics and/or interact with the amyloidogenic region of the protofibril facilitating disaggregation. Significantly, in vitro results on hippocampal cells pointed out protection against glutamate toxicity and safety when administered at low concentrations (1 μM). On the overall, in view of its higher stability in physiological conditions with respect to curcumin, of his rapid binding to fibrillar aggregates and strong depolymerizing activity, phtalimmide derivative K2F21 appeared a good candidate for both AD diagnostic and therapeutic purposes.

2018 - The Effect of Alkaline Cations on the Intercalation of Carbon Dioxide in Sepiolite Minerals: A Molecular Dynamics Investigation [Articolo su rivista]
Tavanti, F.; Muniz-Miranda, F.; Pedone, A.
abstract

The ability of the sepiolite mineral to intercalate CO2 molecules inside its channels in the presence of different alkaline cations (K+, Na+, and Li+) has been studied by classical molecular dynamics simulations. Starting from an alkaline-free sepiolite crystalline model, we built three models with stoichiometry Mg320Si440Al40O1200(OH)160X+40·480H2O. On these models, we gradually replaced the water molecules present in the channels with carbon dioxide and determined the energy of this exchange reaction as well as the structural organization and dynamics of carbon dioxide in the channels. The adsorption energy shows that the Li-containing sepiolite mineral retains more carbon dioxide with respect to those with sodium and potassium cations in the channels. Moreover, the ordered patterns of CO2 molecules observed in the alkaline-free sepiolite mineral are in part destabilized by the presence of cations decreasing the adsorption capacity of this clay mineral.

2017 - Computational Insight into the Interaction of Cytochrome C with Wet and PVP-Coated Ag Surfaces [Articolo su rivista]
Tavanti, Francesco; Pedone, Alfonso; Matteini, Paolo; Menziani, Maria Cristina
abstract

In this work, the adsorption of cytochrome C (CytC) on wet 100, 111, 110, and 120 silver surfaces has been investigated by computational simulations. The effect of polyvinylpyrrolidone (PVP) coating has also been studied. The main results obtained can be summarized as follow: (a) CytC strongly interacts with wet bare high index facets, while the adsorption over the 100 surface is disfavored due to the strong water structuring at the surface; (b) a nonselective protein adsorption mechanism is highlighted; (c) the native structure of CytC is well preserved during adsorption; (d) the heme group of CytC is never found to interact directly with the surface; (e) the interactions with the PVP-capped 100 surface is weak and specific. These results can be exploited to better control biological responses at engineered nanosurface, allowing the development of improved diagnostic tools.

2017 - Experimental and Molecular Dynamics Investigation Proves That Montmorillonite Traps the Biogenic Amines Histamine and Tyramine [Articolo su rivista]
Malferrari, Daniele; Bernini, Fabrizio; Tavanti, Francesco; Tuccio, Luca; Pedone, Alfonso
abstract

Biogenic amines present in high concentrations in foods obtained through fermentation could have toxic effects and contribute to the arising of allergies. For this reason, their removal is of great importance. In this work, we used an experimental and computational approach to investigate the interaction between a calcium montmorillonite, a layered silicate very common in clays, and the two biogenic amines histamine and tyramine, obtaining deep insight into their binding modalities and structural organization. Calcium montmorillonite can exchange almost all its interlayer Ca2+with the protonated histamine and tyramine, thus reducing their concentration in water solution. The adopted multianalytical approach allowed classification of the interaction mechanism as an intercalation. Molecular dynamics simulations showed that the intercalated histamine and tyramine preferentially interact, through the protonated amino nitrogen, with tetrahedral aluminum bearing a net negative charge, whereas interactions with neutral tetrahedral silica is less favorable. We observed that most of histamine molecules bind in the center and above the 6T net of the silica sheet, but for electrostatic constraints they cannot occupy the center of two adjacent 6T nets as occurs for tyramine.

2017 - Site-Selective Surface-Enhanced Raman Detection of Proteins [Articolo su rivista]
Matteini, Paolo; Cottat, Maximilien; Tavanti, Francesco; Panfilova, Elizaveta; Scuderi, Mario; Nicotra, Giuseppe; Menziani, Maria Cristina; Khlebtsov, Nikolai; de Angelis, Marella; Pini, Roberto
abstract

Strategies for protein detection via surface enhanced Raman spectroscopy (SERS) currently exploit the formation of randomly generated hot spots at the interfaces of metal colloidal nanoparticles, which are clustered together by intrusive chemical or physical processes in the presence of the target biomolecule. We propose a different approach based on selective and quantitative gathering of protein molecules at regular hot spots generated on the corners of individual silver nanocubes in aqueous medium at physiological pH. Here, the protein, while keeping its native configuration, experiences an intense local E-field, which boosts SERS efficiency and detection sensitivity. Uncontrolled signal fluctuations caused by variable molecular adsorption to different particle areas or inside clustered nanoparticles are circumvented. Advanced electron microscopy analyses and computational simulations outline a strategy relying on a site-selective mechanism with superior Raman signal enhancement, which offers the perspective of highly controlled and reproducible routine SERS detection of proteins.

2017 - Synthesis, Characterization, and Selective Delivery of DARPin-Gold Nanoparticle Conjugates to Cancer Cells [Articolo su rivista]
Deyev, Sergey; Proshkina, Galina; Ryabova, Anastasiya; Tavanti, Francesco; Menziani, Maria Cristina; Eidelshtein, Gennady; Avishai, Gavriel; Kotlyar, Alexander
abstract

We demonstrate that the designed ankyrin repeat protein (DARPin)_9-29, which specifically targets human epidermal growth factor receptor 2 (HER 2), binds tightly to gold nanoparticles (GNPs). Binding of the protein strongly increases the colloidal stability of the particles. The results of experimental analysis and molecular dynamics simulations show that approximately 35 DARPin_9-29 molecules are bound to the surface of a 5 nm GNP and that the binding does not involve the receptor-binding domain of the protein. The confocal fluorescent microscopy studies show that the DARPin-coated GNP conjugate specifically interacts with the surface of human cancer cells overexpressing epidermal growth factor receptor 2 (HER2) and enters the cells by endocytosis. The high stability under physiological conditions and high affinity to the receptors overexpressed by cancer cells make conjugates of plasmonic gold nanostructures with DARPin molecules promising candidates for cancer therapy.

2016 - Supercritical CO2 Confined in Palygorskite and Sepiolite Minerals: A Classical Molecular Dynamics Investigation [Articolo su rivista]
MUNIZ MIRANDA, Francesco; Lodesani, Federica; Tavanti, Francesco; Presti, Davide; Malferrari, Daniele; Pedone, Alfonso
abstract

We have investigated the ability of two modular phyllosilicates (palygorskite and sepiolite) to store CO2 molecules inside their structural channels by means of classical molecular dynamics. Several models containing an increasing supercritical-CO2/H2O ratio into the phyllosilicate channels have been built and the structural and dynamic properties of carbon dioxide and water molecules investigated in detail. We found that both clay minerals can achieve this goal, with sepiolite being able to store more carbon dioxide molecules (and more stably) than palygorskite, due to the larger channels of the former. Interestingly, with the increase of CO2 molecules inside the minerals, the diffusivity of both water and carbon dioxide drastically decreases and carbon dioxide molecules tend to arrange themselves in an ordered pattern. (Figure Presented).

2015 - A closer look into the ubiquitin corona on gold nanoparticles by computational studies [Articolo su rivista]
Tavanti, Francesco; Pedone, Alfonso; Menziani, Maria Cristina
abstract

In this study, coarse-grained computational simulations of the ubiquitin corona around gold nanoparticles have been carried out, and the effect of the nanoparticle size (10, 16, 20, and 24 nm diameter) and environment (bare nanoparticle surface, and citrate-coated surface, where citrate are treated with implicit and explicit models) has been analysed. The results showed that the corona is obtained after a slow reorientation step that occurs at the nanoparticle surface in order to optimize the nanoparticle–ubiquitins interaction. The ubiquitin binding modalities depend on the nanoparticle environment, while conformational changes of ubiquitins upon binding and their aggregation propensity slightly depend on nanoparticle size.

2015 - Competitive Binding of Proteins to Gold Nanoparticles Disclosed by Molecular Dynamics Simulations [Articolo su rivista]
Tavanti, Francesco; Pedone, Alfonso; Menziani, Maria Cristina
abstract

Abstract This work reports the results of coarse-grained molecular dynamics simulations of citrate-coated gold nanoparticles (AuNPs) in interaction with insulin and fibrinogen, two of the most abundant proteins in the plasma. The following have been found: (a) The corona of citrate-coated AuNP of 5 nm core diameter is composed by a single layer of proteins comprising a maximum of 20 insulins, whereas only 3 fibrinogens are contemporaneously present. (b) The binding site for insulin is specific and independent from the number of insulins considered in the computational simulations, whereas fibrinogen presents different binding modes, as a function of protein concentration and composition. Moreover, fibrinogen is able to accommodate two citrate-coated AuNPs in independent binding sites localized at the ending nodes. (c) A competitve process for AuNP binding is observed when insulins and fibrinogens are contemporaneously present in the simulations. (d) The overall protein secondary structure is maintained upon binding to a single citrate-coated AuNP, but small changes in helix and sheet percentages are observed for both proteins. (e) A partial unfolding of the α-helix bundle is found for fibrinogen bound to two AuNPs. This may provide a molecular level understanding of the inflammatory response to nanoparticles. © 2015 American Chemical Society.