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1.
Chemosphere ; 282: 131121, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34470166

RESUMO

Microplastic (MP) pollution causes global concerns regarding the consequential impacts on human health. In particular, MPs may act as vectors for various contaminants to induce adverse effects in human. In this work, the joint cytotoxicity of two different MPs co-exposed with diverse ionic pollutants was investigated in two cell lines from human digestive system: human gastric epithelium (GES-1) and colorectal mucosa (FHC) cell lines. The results indicated that the cytotoxicity of cationic pollutants was alleviated by MPs more significantly than that of anionic pollutants in both culture medium and river water. The electrostatic attraction between the negatively charged MPs and cations was a key factor in determining the ultimate joint toxicity. Our findings indicate that the joint cytotoxicity of MP-pollutant mixtures may be proactively reduced by modulating the surface charge of MPs.


Assuntos
Poluentes Ambientais , Poluentes Químicos da Água , Cátions , Humanos , Microplásticos , Plásticos , Eletricidade Estática , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
2.
Mater Sci Eng C Mater Biol Appl ; 128: 112294, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474845

RESUMO

In the present study, new-layered inorganic/organic hybrid of silver/talc nanocomposites (Ag/Tlc-NPs) and its chitosan-capped derivative (Ag/Tlc/Csn NCs) were biochemically synthesized utilizing Lawsonia inermis L. extract. The silver nanoparticles (Ag NPs) were synthesized employing green method on the exterior surface layer of talc mineral as a solid substrate. The negatively charged surface layer of talc might function as templates and can attract the chitosan cations from a solution to yield a layered hybrid structure, whose inorganic phase is formed by Si-O-Ag bonds. Our results revealed that Ag NPs were formed on the exterior surface of talc with a diameter with size of 124-215 nm. In addition, cytotoxicity, in vitro antibacterial activity, and clinical effects of wound-healing ointments containing talc were investigated. The results implied the successful synthesis of Ag/Tlc/Csn NCs using the extract. The structures were safe up to 0.50 mg/mL. In vitro studies confirmed antioxidant and antibacterial properties of Ag/Tlc/Csn NCs. In sum, our findings showed that the ointments improve wound healing process by inducing an anti-inflammatory M2 phenotype and bFGF, CD206, collagen1A, and IL-10 production that causes fibroblast migration and wound closure through influencing M2 macrophage. Ag/Tlc/Csn is suggested to be taken into consideration as a medical combination for improving infected wound healing and as a promising agent for clinical administration.


Assuntos
Quitosana , Lawsonia (Planta) , Nanopartículas Metálicas , Nanocompostos , Aceleração , Antibacterianos/farmacologia , Pseudomonas aeruginosa , Prata , Staphylococcus aureus , Eletricidade Estática , Talco , Cicatrização
3.
Anal Chim Acta ; 1177: 338766, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34482895

RESUMO

Among the most toxic and suffocating gases in industries and mines are carbon monoxide (CO) and nitrogen oxides (NOx). The electrostatically functionalized self-assembled MWCNT (f-MWCNTs) were employed to develop a sensing device to selectively sense gases such as CO and NOx with high sensitivity and repeatability to as low as sub-ppm levels. The resistive gas sensor's operation is primarily based on changes in the electrical resistance of the f-MWCNT network as a result of its selective interaction with the specific target gas in a two-pole format. The degree to which the electrical resistance of the sensing film increases or decreases is determined by the concentration of the target gas to which it is exposed. As a result, the target gas can be detected both qualitatively and quantitatively. The sensitivity of 100 ppb and 300 ppb with the sensor response time of ∼30 s and ∼50 s for NOx and CO respectively were recorded using our gas sensor and was found noticeably efficient than conventional MOS-based solid-state gas detectors. It was also realized that the corona-assisted, electrostatic, self-assembled MWCNT based sensor fabrication technique is fast, simple, low-cost, and environmentally friendly for commercial-scale production of gas sensors. This approach also extends many technical merits such as simultaneous deposition and functionalization of MWCNTs at (RT = 30 °C) room temperature for specific target analyte detection. These unique characteristics make f-MWCNTs based devices very appealing for real-time commercial and domestic gas sensing applications.


Assuntos
Doenças Cardiovasculares , Nanotubos de Carbono , Humanos , Óxidos de Nitrogênio , Eletricidade Estática , Temperatura
4.
Langmuir ; 37(34): 10394-10401, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34403253

RESUMO

Fibrinogen (Fg) self-assembly is sensitive to the physicochemical properties of an environment like pH and ionic strength. These parameters tune the direction and strength of noncovalent physical driving forces determining protein intermolecular interactions. The attraction-repulsion balance in intermolecular interactions of the multidomain protein Fg at pH values 3.5, 7.4, and 9.5 and varying ionic strengths of the water medium has been analyzed by the complex diffusive approach, proposed by us previously. The concentration dependence of protein collective diffusion was analyzed within the phenomenological approach, based on the frictional formalism of nonequilibrium thermodynamics proposed by H. Vink. The analysis of protein diffusion data has shown the fundamental difference in the physical nature and direction of interaction forces between protein molecules at different conditions. The paired interaction potential of protein molecules was characterized in terms of second virial coefficients and Hamaker constants within the Deryaguin-Landau-Verwey-Overbeek theory and the "porous" colloid particle model. Our results indicated the maximum Hamaker constant and dominance of the van der Waals attraction between Fg molecules at pH 7.4. The increase in pH up to 9.5 results in the zero values of the second virial coefficient and Hamaker constant, corresponding to the full reciprocal compensation for electrostatic repulsion and van der Waals attraction. In the acidic medium (pH 3.5), the strong electrostatic repulsion substantially exceeds the van der Waals attraction. A high ionic strength is characterized by a significant decrease of all intermolecular interactions, which is expressed in almost zero values of virial coefficients and the Hamaker constant. Thus, it is experimentally shown that the physiological conditions of the Fg environment (pH 7.4 and slight ionic strength) provide a high probability for peak physical attraction between fibrinogen molecules, which is used in nature to facilitate blood clotting.


Assuntos
Fibrinogênio , Concentração de Íons de Hidrogênio , Concentração Osmolar , Eletricidade Estática , Termodinâmica
5.
Molecules ; 26(15)2021 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-34361639

RESUMO

Many experiments have been carried out to display different colors of Proteorhodopsin (PR) and its mutants, but the mechanism of color tuning of PR was not fully elucidated. In this study, we applied the Electrostatically Embedded Generalized Molecular Fractionation with Conjugate Caps (EE-GMFCC) method to the prediction of excitation energies of PRs. Excitation energies of 10 variants of Blue Proteorhodopsin (BPR-PR105Q) in residue 105GLN were calculated with the EE-GMFCC method at the TD-B3LYP/6-31G* level. The calculated results show good correlation with the experimental values of absorption wavelengths, although the experimental wavelength range among these systems is less than 50 nm. The ensemble-averaged electric fields along the polyene chain of retinal correlated well with EE-GMFCC calculated excitation energies for these 10 PRs, suggesting that electrostatic interactions from nearby residues are responsible for the color tuning. We also utilized the GMFCC method to decompose the excitation energy contribution per residue surrounding the chromophore. Our results show that residues ASP97 and ASP227 have the largest contribution to the absorption spectral shift of PR among the nearby residues of retinal. This work demonstrates that the EE-GMFCC method can be applied to accurately predict the absorption spectral shifts for biomacromolecules.


Assuntos
Simulação de Dinâmica Molecular , Teoria Quântica , Rodopsinas Microbianas/química , Eletricidade Estática
6.
Molecules ; 26(16)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34443491

RESUMO

Glycyrrhetic acid (GA) and stearyl glycyrrhetinate (SG) are two interesting compounds from Glycyrrhiza glabra, showing numerous biological properties widely applied in the pharmaceutical and cosmetic fields. Despite these appreciable benefits, their potential therapeutic properties are strongly compromised due to unfavourable physical-chemical features. The strategy exploited in the present work was to develop solid lipid nanoparticles (SLNs) as carrier systems for GA and SG delivery. Both formulations loaded with GA and SG (GA-SLNs and SG-SLNs, respectively) were prepared by the high shear homogenization coupled to ultrasound (HSH-US) method, and we obtained good technological parameters. DSC was used to evaluate their thermotropic behaviour and ability to act as carriers for GA and SG. The study was conducted by means of a biomembrane model (multilamellar vesicles; MLVs) that simulated the interaction of the carriers with the cellular membrane. Unloaded and loaded SLNs were incubated with the biomembranes, and their interactions were evaluated over time through variations in their calorimetric curves. The results of these studies indicated that GA and SG interact differently with MLVs and SLNs; the interactions of SG-SLNs and GA-SLNs with the biomembrane model showed different variations of the MLVs calorimetric curve and suggest the potential use of SLNs as delivery systems for GA.


Assuntos
Calorimetria , Ácido Glicirretínico/análogos & derivados , Ácido Glicirretínico/farmacologia , Lipídeos/química , Nanopartículas/química , Ácido Glicirretínico/química , Cinética , Membranas , Eletricidade Estática , Temperatura de Transição
7.
Int J Mol Sci ; 22(15)2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34361016

RESUMO

Although small water clusters (SWCs) are important in many research fields, efficient methods of preparing SWCs are still rarely reported, which is mainly due to the lack of related materials and understanding of the molecular interaction mechanisms. In this study, a series of functional molecules were added in water to obtain small water cluster systems. The decreasing rate of the half-peak width in a sodium dodecyl sulfate (SDS)-water system reaches ≈20% at 0.05 mM from 17O nuclear magnetic resonance (NMR) results. Based on density functional theory (DFT) and molecular dynamics (MD) simulation calculation, it can be concluded that functional molecules with stronger negative electrostatic potential (ESP) and higher hydrophilicity have a stronger ability to destroy big water clusters. Notably, the concentrations of our selected molecule systems are one to two magnitudes lower than that of previous reports. This study provides a promising way to optimize aqueous systems in various fields such as oilfield development, protein stability, and metal anti-corrosion.


Assuntos
Interações Hidrofóbicas e Hidrofílicas , Simulação de Dinâmica Molecular , Dodecilsulfato de Sódio/química , Espectroscopia de Ressonância Magnética , Eletricidade Estática , Água/química
8.
Langmuir ; 37(33): 10020-10028, 2021 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34375117

RESUMO

Most marine antifouling coatings rely on the release of toxic biocides to prevent fouling organisms from attaching, causing environmental pollution. This work proposes a biocide-free environmentally friendly marine antifouling strategy. Slippery-liquid-infused electrostatic flocking surfaces (S-EFSs) were prepared by combining electrostatic flocking and slippery liquid infusion. They exhibited complete mussel resistance after comparing adhesion to the surface of different materials in the laboratory. In addition, the unique surface morphology including lubricant was found to be crucial to their antifouling performance. Real-time polymerase chain reaction showed that different surfaces significantly affected the gene-expression levels of the mussels' foot proteins, where higher levels on S-EFSs meant that the mussels tried to secrete more proteins but they failed to adhere. Moreover, a 148-day field test showed that S-EFSs can resist not only mussels but also tubeworms, tunicates, and barnacles, and the total fouling area decreased by more than 50% compared to control samples. Notably, the maturity of electrostatic flocking technology and the simplicity of the modification steps used endow this strategy with the potential to significantly reduce the economic loss caused by marine biofouling in practical applications.


Assuntos
Incrustação Biológica , Desinfetantes , Thoracica , Animais , Incrustação Biológica/prevenção & controle , Desinfetantes/toxicidade , Eletricidade Estática , Propriedades de Superfície
9.
Molecules ; 26(16)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34443412

RESUMO

Palmarosa essential oil (PEO) is an alternative to synthetic fungicides to control the contamination by food-deteriorating fungi, such as Aspergillus nomius. Nonetheless, the low long-term stability and volatility hamper its utilization. Thus, this study aimed to develop nanostructured lipid carriers (NLCs) containing PEO to improve its stability and consequently prolong the activity against A. nomius. A mixture design was applied to find the best preparation conditions for antifungal activity. The characterization analyses included size measurements, zeta potential (ζ-potential), entrapment efficiency (EE), and antifungal activity (by inhibition of mycelial growth (IMG) and/or in situ test (pre-contaminated Brazil nuts) tests). The nanocarriers presented particle sizes smaller than 300 nm, homogeneous size distribution, ζ-potential of -25.19 to -41.81 mV, and EE between 73.6 and 100%. The formulations F5 and F10 showed the highest IMG value (98.75%). Based on the regression model, three optimized formulations (OFs) were tested for antifungal activity (IMG and in situ test), which showed 100% of inhibition and prevented the deterioration of Brazil nuts by A. nomius. The preliminary stability test showed the maintenance of antifungal activity and physicochemical characteristics for 90 days. These results suggest a promising system as a biofungicide against A. nomius.


Assuntos
Aspergillus/efeitos dos fármacos , Cymbopogon/química , Portadores de Fármacos/química , Nanoestruturas/química , Óleos Voláteis/farmacologia , Antifúngicos/farmacologia , Bertholletia/microbiologia , Composição de Medicamentos , Cromatografia Gasosa-Espectrometria de Massas , Testes de Sensibilidade Microbiana , Nanoestruturas/ultraestrutura , Tamanho da Partícula , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática
10.
Langmuir ; 37(35): 10424-10432, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34427433

RESUMO

Core-shell microcapsules with combined features of hydrophilicity and hydrophobicity have become much popular. However, the assembly of biocompatible and edible materials in hydrophilic-hydrophobic core-shell microcapsules is not easy. In this work, based on electrostatic interactions, we prepared controllable calcium alginate (ALG)-zein core-shell particles of different shapes and sizes using hydrophilic ALG and hydrophobic zein by a two-step extrusion method. Negatively charged hydrogel beads of spherical, ellipsoidal, or fibrous shape were added into a positively charged zein solution (dissolved in 70% (v/v) aqueous ethanol solution) to achieve different-shaped core-shell particles. Interestingly, the size, shape, and shell thickness of the particles can be regulated by the needle diameter, stirring speed, and zein concentration. Moreover, for simplification, the core-shell particles were also synthesized by a one-step extrusion method, in which an ALG solution was added dropwise into a 70% (v/v) aqueous ethanol solution containing zein and CaCl2. The particles synthesized in this work showed controlled digestion of encapsulated medium-chain triglyceride (MCT) and sustained release of encapsulated thiamine and ethyl maltol. Our preparation method is simplistic and can be extended to fabricate a variety of hydrophilic and hydrophobic core-shell structures to encapsulate a broad spectrum of materials.


Assuntos
Zeína , Alginatos , Cápsulas , Interações Hidrofóbicas e Hidrofílicas , Eletricidade Estática
11.
Viruses ; 13(8)2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34452480

RESUMO

We compared the electrostatic properties of the spike proteins (S-proteins) of three coronaviruses, SARS-CoV, MERS-CoV, and SARS-CoV-2, and their interactions with photosensitizers (PSs), octacationic octakis(cholinyl)zinc phthalocyanine (Zn-PcChol8+) and monocationic methylene blue (MB). We found a major common PS binding site at the connection of the S-protein stalk and head. The molecules of Zn-PcChol8+ and MB also form electrostatic encounter complexes with large area of negative electrostatic potential at the head of the S-protein of SARS-CoV-2, between fusion protein and heptad repeat 1 domain. The top of the SARS-CoV spike head demonstrates a notable area of electrostatic contacts with Zn-PcChol8+ and MB that corresponds to the N-terminal domain. The S-protein protomers of SARS-CoV-2 in "open" and "closed" conformations demonstrate different ability to attract PS molecules. In contrast with Zn-PcChol8+, MB possesses the ability to penetrate inside the pocket formed as a result of SARS-CoV-2 receptor binding domain transition into the "open" state. The existence of binding site for cationic PSs common to the S-proteins of SARS-CoV, SARS-CoV-2, and MERS-CoV creates prospects for the wide use of this type of PSs to combat the spread of coronaviruses.


Assuntos
Indóis/metabolismo , Coronavírus da Síndrome Respiratória do Oriente Médio/química , Compostos Organometálicos/metabolismo , Fármacos Fotossensibilizantes/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Sítios de Ligação , Indóis/química , Azul de Metileno/metabolismo , Modelos Moleculares , Simulação de Dinâmica Molecular , Compostos Organometálicos/química , Conformação Proteica , Domínios Proteicos , Subunidades Proteicas/química , Vírus da SARS/química , SARS-CoV-2/química , Glicoproteína da Espícula de Coronavírus/química , Eletricidade Estática
12.
Molecules ; 26(16)2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34443692

RESUMO

In this study, time-dependent, one-dimensional modeling of a surface dielectric barrier discharge (SDBD) device, driven by a sinusoidal voltage of amplitude 1-3 kV at 20 kHz, in argon is described. An SDBD device with two Cu-stripe electrodes, covered by the quartz dielectric and with the discharge gap of 20 × 10-3 m, was assumed, and the time-dependent, one-dimensional discharge parameters were simulated versus time across the plasma gap. The plasma device simulated in the given arrangement was constructed and used for biocompatible antibacterial/antimicrobial coating of plasmonic particle aerosol and compared with the coating strategy of the DBD plasma jet. Simulation results showed discharge consists of an electrical breakdown, occurring in each half-cycle of the AC voltage with an electron density of 1.4 × 1010 cm-3 and electric field strength of 4.5 × 105 Vm-1. With SDBD, the surface coating comprises spatially distributed particles of mean size 29 (11) nm, while with argon plasma jet, the nanoparticles are aggregated in clusters that are three times larger in size. Both coatings are crystalline and exhibit plasmonic features in the visible spectral region. It is expected that the particle aerosols are collected under the ionic wind, induced by the plasma electric fields, and it is assumed that this follows the dominant charging mechanisms of ions diffusion. The cold plasma strategy is appealing in a sense; it opens new venues at the nanoscale to deal with biomedical and surgical devices in a flexible processing environment.


Assuntos
Materiais Biocompatíveis/química , Simulação por Computador , Modelos Teóricos , Nanopartículas/química , Gases em Plasma/química , Aerossóis/análise , Eletrodos , Nanopartículas/ultraestrutura , Tamanho da Partícula , Eletricidade Estática , Temperatura , Fatores de Tempo
13.
J Phys Chem Lett ; 12(32): 7818-7825, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34378946

RESUMO

Intramolecular vibrational energy relaxation (IVR) is fundamentally important to chemical dynamics. We show that externally applied electric fields affect IVR and vibrational line widths by changing the anharmonic couplings and frequency detunings between modes. We demonstrate this effect in benzonitrile for which prior experimental results show a decrease in vibrational line width as a function of applied electric field. We identify three major channels for IVR that depend on electric field. In the dominant channel, the electric field affects the frequency detuning, while in the other two channels, variation of anharmonic couplings as a function of field is the underlying mechanism. Consistent with experimental results, we show that the combination of all channels gives rise to reduced line widths with increasing electric field in benzonitrile. Our results are relevant for controlling IVR with external or internal fields and for gaining a more complete interpretation of line widths of vibrational Stark probes.


Assuntos
Nitrilas/química , Eletricidade Estática , Vibração , Transferência de Energia
14.
Nat Commun ; 12(1): 5106, 2021 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34429434

RESUMO

The cytoplasmic domain of PD-L1 (PD-L1-CD) regulates PD-L1 degradation and stability through various mechanism, making it an attractive target for blocking PD-L1-related cancer signaling. Here, by using NMR and biochemical techniques we find that the membrane association of PD-L1-CD is mediated by electrostatic interactions between acidic phospholipids and basic residues in the N-terminal region. The absence of the acidic phospholipids and replacement of the basic residues with acidic residues abolish the membrane association. Moreover, the basic-to-acidic mutations also decrease the cellular abundance of PD-L1, implicating that the electrostatic interaction with the plasma membrane mediates the cellular levels of PD-L1. Interestingly, distinct from its reported function as an activator of AMPK in tumor cells, the type 2 diabetes drug metformin enhances the membrane dissociation of PD-L1-CD by disrupting the electrostatic interaction, thereby decreasing the cellular abundance of PD-L1. Collectively, our study reveals an unusual regulatory mechanism that controls the PD-L1 level in tumor cells, suggesting an alternative strategy to improve the efficacy of PD-L1-related immunotherapies.


Assuntos
Antígeno B7-H1/metabolismo , Membranas/metabolismo , Eletricidade Estática , Antígeno B7-H1/química , Antígeno B7-H1/genética , Membrana Celular/metabolismo , Diabetes Mellitus Tipo 2 , Células HEK293 , Humanos , Imunoterapia , Metformina , Mutação
15.
Nat Commun ; 12(1): 4710, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34354070

RESUMO

Cyanophage S-2L is known to profoundly alter the biophysical properties of its DNA by replacing all adenines (A) with 2-aminoadenines (Z), which still pair with thymines but with a triple hydrogen bond. It was recently demonstrated that a homologue of adenylosuccinate synthetase (PurZ) and a dATP triphosphohydrolase (DatZ) are two important pieces of the metabolism of 2-aminoadenine, participating in the synthesis of ZTGC-DNA. Here, we determine that S-2L PurZ can use either dATP or ATP as a source of energy, thereby also depleting the pool of nucleotides in dATP. Furthermore, we identify a conserved gene (mazZ) located between purZ and datZ genes in S-2L and related phage genomes. We show that it encodes a (d)GTP-specific diphosphohydrolase, thereby providing the substrate of PurZ in the 2-aminoadenine synthesis pathway. High-resolution crystal structures of S-2L PurZ and MazZ with their respective substrates provide a rationale for their specificities. The Z-cluster made of these three genes - datZ, mazZ and purZ - was expressed in E. coli, resulting in a successful incorporation of 2-aminoadenine in the bacterial chromosomal and plasmidic DNA. This work opens the possibility to study synthetic organisms containing ZTGC-DNA.


Assuntos
DNA Bacteriano/genética , Genes Virais , Siphoviridae/genética , 2-Aminopurina/análogos & derivados , 2-Aminopurina/metabolismo , Adenilossuccinato Sintase/química , Adenilossuccinato Sintase/genética , Adenilossuccinato Sintase/metabolismo , Bacteriófagos , Pareamento de Bases , Cristalografia por Raios X , DNA Bacteriano/metabolismo , DNA Viral/genética , DNA Viral/metabolismo , Desoxiadenosinas/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Genoma Viral , Redes e Vias Metabólicas , Modelos Moleculares , Monoéster Fosfórico Hidrolases/química , Monoéster Fosfórico Hidrolases/genética , Monoéster Fosfórico Hidrolases/metabolismo , Podoviridae/classificação , Podoviridae/genética , Conformação Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Siphoviridae/classificação , Eletricidade Estática , Proteínas Virais/química , Proteínas Virais/genética , Proteínas Virais/metabolismo
16.
J Chem Phys ; 155(5): 055102, 2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34364335

RESUMO

Ratcheted multi-step hopping electron transfer systems can plausibly produce directional charge transport over very large distances without requiring a source-drain voltage bias. We examine molecular strategies to realize ratcheted charge transport based on multi-step charge hopping, and we illustrate two ratcheting mechanisms with examples based on DNA structures. The charge transport times and currents that may be generated in these assemblies are also estimated using kinetic simulations. The first ratcheting mechanism described for nanoscale systems requires local electric fields on the 109 V/m scale to realize nearly 100% population transport. The second ratcheting mechanism for even larger systems, based on electrochemical gating, is estimated to generate currents as large as 0.1 pA for DNA structures that are a few µm in length with a gate voltage of about 5 V, a magnitude comparable to currents measured in DNA wires at the nanoscale when a source-drain voltage bias of similar magnitude is applied, suggesting an approach to considerably extend the distance range over which DNA charge transport devices may operate.


Assuntos
DNA/química , Nanoestruturas/química , Condutividade Elétrica , Eletroquímica , Cinética , Eletricidade Estática
17.
Phys Chem Chem Phys ; 23(32): 17656-17662, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34373871

RESUMO

In this manuscript the ability of selenium carbohydrates to undergo chalcogen bonding (ChB) interactions with protein residues has been studied at the RI-MP2/def2-TZVP level of theory. An inspection of the Protein Data Bank (PDB) revealed SeA (A = O, C and S) intermolecular contacts involving Se-pyranose ligands and ASP, TYR, SER and MET residues. Theoretical models were built to analyse the strength and directionality of the interaction together with "Atoms in Molecules" (AIM), Natural Bonding Orbital (NBO) and Non Covalent Interactions plot (NCIplot) analyses, which further assisted in the characterization of the ChBs described herein. We expect that the results from this study will be useful to expand the current knowledge regarding biological ChBs as well as to increase the visibility of the interaction among the carbohydrate chemistry community.


Assuntos
Lectinas/metabolismo , Monossacarídeos/metabolismo , Compostos Organosselênicos/metabolismo , Agaricales/química , Aspergillus oryzae/química , Bases de Dados de Proteínas , Escherichia coli/química , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/metabolismo , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Ligação de Hidrogênio , Lectinas/química , Modelos Moleculares , Monossacarídeos/química , Compostos Organosselênicos/química , Ligação Proteica , Selênio/química , Eletricidade Estática , Termodinâmica
18.
J Phys Chem B ; 125(27): 7368-7379, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34228472

RESUMO

A structural understanding of the mechanism by which antibodies bind SARS-CoV-2 at the atomic level is highly desirable as it can tell the development of more effective antibodies to treat Covid-19. Here, we use steered molecular dynamics (SMD) and coarse-grained simulations to estimate the binding affinity of the monoclonal antibodies CR3022 and 4A8 to the SARS-CoV-2 receptor-binding domain (RBD) and SARS-CoV-2 N-terminal domain (NTD). Consistent with experiments, our SMD and coarse-grained simulations both indicate that CR3022 has a higher affinity for SARS-CoV-2 RBD than 4A8 for the NTD, and the coarse-grained simulations indicate the former binds three times stronger to its respective epitope. This finding shows that CR3022 is a candidate for Covid-19 therapy and is likely a better choice than 4A8. Energetic decomposition of the interaction energies between these two complexes reveals that electrostatic interactions explain the difference in the observed binding affinity between the two complexes. This result could lead to a new approach for developing anti-Covid-19 antibodies in which good candidates must contain charged amino acids in the area of contact with the virus.


Assuntos
COVID-19 , Glicoproteína da Espícula de Coronavírus , Anticorpos Antivirais , Humanos , SARS-CoV-2 , Eletricidade Estática
19.
J Phys Chem B ; 125(27): 7351-7358, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34213353

RESUMO

Cationic or anionic residues are frequently located at the termini of proteins because their charged side chain can form electrostatic interactions with a terminal carboxylate or ammonium group to stabilize the structure under physiological conditions. Here, we used collagen-mimetic peptides (CMPs) to examine how the terminal charge-charge interactions affect the collagen triple helix stability. We designed a series of CMPs with either a Lys or Glu incorporated into the terminus and measured their pH-dependent stability. The results showed that the terminal electrostatic attractions stabilized the triple helix, while the terminal electrostatic repulsions destabilized the trimer. The data also revealed that the repulsions imposed a greater effect than did the attractions on the triple helix. An amino acid with a shorter side chain, such as aspartate and ornithine, was also installed to investigate the length effect on electrostatic interactions, which was found to be insignificant. Meanwhile, simultaneously incorporating cationic and anionic residues into the termini showed slight additive stabilization effects but pronounced additive destabilization consequences. We have demonstrated that the collagen triple helix stability can be modulated by introducing a cationic or anionic residue into the terminus of a peptide, giving useful information for the design of collagen-associated materials.


Assuntos
Colágeno , Peptídeos , Aminoácidos , Dicroísmo Circular , Eletricidade Estática
20.
Biophys J ; 120(15): 2998-3007, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34214536

RESUMO

Protein-protein interactions underlie many critical biology functions, such as cellular signaling and gene expression, in which electrostatic interactions can play a critical role in mediating the specificity and stability of protein complexes. A substantial portion of proteins are intrinsically disordered, and the influences of structural disorder on binding kinetics and thermodynamics have been widely investigated. However, whether the effect of electrostatic steering depends on structural disorder remains unexplored. In this work, we addressed the consequence of introducing intrinsic disorder in the electrostatic steering of the E3/Im3 complex using molecular dynamics simulation. Our results recapitulated the experimental observations that the responses of stability and kinetics to salt concentration for the ordered E3/Im3 complex were larger than those for the disordered E3/Im3 complex. Mechanistic analysis revealed that the native contact interactions involved in the encounter state and the transition state were essentially identical for both ordered and disordered E3. Therefore, the observed difference in electrostatic steering between ordered E3 and disordered E3 may result from their difference in conformation rather than their difference in binding mechanism. Because charged residues are frequently involved in protein-protein interactions, our results suggest that increasing structural disorder is expected to generally modulate the effect of electrostatic steering.


Assuntos
Proteínas Intrinsicamente Desordenadas , Proteínas Intrinsicamente Desordenadas/metabolismo , Cinética , Simulação de Dinâmica Molecular , Ligação Proteica , Conformação Proteica , Dobramento de Proteína , Eletricidade Estática , Termodinâmica
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