RESUMO
The design of RNA sequences with desired structural properties presents a challenging computational problem with promising applications in biotechnology and biomedicine. Most regulatory RNAs function by forming RNA-RNA interactions, e.g., in order to regulate mRNA expression. It is therefore natural to consider problems where a sequence is designed to form a desired RNA-RNA interaction and switch between structures upon binding. This contribution demonstrates the use of the Infrared framework to design interacting sequences. Specifically, we consider the regulation of the rpoS mRNA by the sRNA DsrA and design artificial 5 ' UTRs that place a downstream protein coding gene under control of DsrA. The design process is explained step by step in a Jupyter notebook, accompanied by Python code. The text discusses setting up design constraints for sampling sequences in Infrared, computing quality measures, constructing a suitable cost function, as well as the optimization procedure. We show that not only thermodynamic but also kinetic folding features can be relevant. Kinetics of interaction formation can be estimated efficiently using the RRIkinDP tool, and the chapter explains how to include kinetic folding features from RRIkinDP directly in the cost function. The protocol implemented in our Jupyter notebook can easily be extended to consider additional requirements or adapted to novel design scenarios.
Assuntos
Conformação de Ácido Nucleico , Termodinâmica , Biologia Computacional/métodos , Software , Cinética , RNA/genética , RNA/química , RNA/metabolismo , Regiões 5' não Traduzidas , RNA Mensageiro/genética , RNA Mensageiro/química , RNA Mensageiro/metabolismo , Algoritmos , Dobramento de RNARESUMO
In this study, the interaction of the human hemoglobin with cost effective and chemically fabricated CdS quantum dots (QDs) (average sizes ≈3nm) has been investigated. The semiconductor QDs showed maximum visible absorption at 445 nm with excitonic formation and band gap of ≈ 2.88 eV along with hexagonal crystalline phase. The binding of QDs-Hb occurs through corona formation to the ground sate complex formation. The life time of the heme pocket binding and reorganization were found to be t1 = 43 min and t2 = 642 min, respectively. The emission quenching of the Hb has been indicated large energy transfer between CdS QDs and Hb with tertiary deformation of Hb. The binding thermodynamics showed highly exothermic nature. The ultrafast decay during corona formation was studied from TCSPC. The results showed that the energy transfer efficiency increases with the increase of the QDs concentration and maximum ≈71.5 % energy transfer occurs and average ultrafast lifetime varies from 5.45 ns to1.51 ns. The deformation and unfolding of the secondary structure of Hb with changes of the α-helix (≈74 % to ≈51.07 %) and ß-sheets (≈8.63 % to ≈10.25 %) have been observed from circular dichroism spectrum. The SAXS spectrum showed that the radius of gyration of CdS QDs-Hb bioconjugate increased (up to 23 ± 0.45 nm) with the increase of the concentration of QDs compare with pure Hb (11 ± 0.23 nm) and Hb becoming more unfolded.
Assuntos
Compostos de Cádmio , Transferência de Energia , Hemoglobinas , Desdobramento de Proteína , Pontos Quânticos , Sulfetos , Pontos Quânticos/química , Humanos , Compostos de Cádmio/química , Sulfetos/química , Sulfetos/metabolismo , Hemoglobinas/química , Hemoglobinas/metabolismo , Ligação Proteica , Termodinâmica , Espectrometria de Fluorescência , Dicroísmo CircularRESUMO
Thermodynamic modeling is still the most widely used method to characterize aerosol acidity, a critical physicochemical property of atmospheric aerosols. However, it remains unclear whether gas-aerosol partitioning should be incorporated when thermodynamic models are employed to estimate the acidity of coarse particles. In this work, field measurements were conducted at a coastal city in northern China across three seasons, and covered wide ranges of temperature, relative humidity and NH3 concentrations. We examined the performance of different modes of ISORROPIA-II (a widely used aerosol thermodynamic model) in estimating aerosol acidity of coarse and fine particles. The M0 mode, which incorporates gas-phase data and runs the model in the forward mode, provided reasonable estimation of aerosol acidity for coarse and fine particles. Compared to M0, the M1 mode, which runs the model in the forward mode but does not include gas-phase data, may capture the general trend of aerosol acidity but underestimates pH for both coarse and fine particles; M2, which runs the model in the reverse mode, results in large errors in estimated aerosol pH for both coarse and fine particles and should not be used for aerosol acidity calculations. However, M1 significantly underestimates liquid water contents for both fine and coarse particles, while M2 provides reliable estimation of liquid water contents. In summary, our work highlights the importance of incorporating gas-aerosol partitioning when estimating coarse particle acidity, and thus may help improve our understanding of acidity of coarse particles.
Assuntos
Aerossóis , Poluentes Atmosféricos , Modelos Químicos , Termodinâmica , Aerossóis/análise , Aerossóis/química , Poluentes Atmosféricos/química , Poluentes Atmosféricos/análise , China , Monitoramento Ambiental/métodos , Material Particulado/química , Material Particulado/análise , Concentração de Íons de Hidrogênio , Tamanho da PartículaRESUMO
A cell's fate involves transitions among its various states, each defined by a distinct gene expression profile governed by the topology of gene regulatory networks, which are affected by 3D genome organization. Here, we develop thermodynamic models to determine the fate of a malignant cell as governed by the tumor suppressor p53 signaling network, taking into account long-range chromatin interactions in the mean-field approximation. The tumor suppressor p53 responds to stress by selectively triggering one of the potential transcription programs that influence many layers of cell signaling. These range from p53 phosphorylation to modulation of its DNA binding affinity, phase separation phenomena, and internal connectivity among cell fate genes. We use the minimum free energy of the system as a fundamental property of biological networks that influences the connection between the gene network topology and the state of the cell. We constructed models based on network topology and equilibrium thermodynamics. Our modeling shows that the binding of phosphorylated p53 to promoters of target genes can have properties of a first order phase transition. We apply our model to cancer cell lines ranging from breast cancer (MCF-7), colon cancer (HCT116), and leukemia (K562), with each one characterized by a specific network topology that determines the cell fate. Our results clarify the biological relevance of these mechanisms and suggest that they represent flexible network designs for switching between developmental decisions.
Assuntos
Termodinâmica , Proteína Supressora de Tumor p53 , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Humanos , Redes Reguladoras de Genes , Modelos Biológicos , Fosforilação , Linhagem Celular Tumoral , Transdução de SinaisRESUMO
Protein kinase R (PKR) functions in the eukaryotic innate immune system as a first-line defense against viral infections. PKR binds viral dsRNA, leading to autophosphorylation and activation. In its active state, PKR can phosphorylate its primary substrate, eIF2α, which blocks the initiation of translation in the infected cell. It has been established that PKR activation occurs when the kinase domain dimerizes in a back-to-back configuration. However, the mechanism by which dimerization leads to enzymatic activation is not fully understood. Here, we investigate the structural mechanistic basis and energy landscape for PKR activation, with a focus on the αC helixâa kinase activation and signal integration hubâusing all-atom equilibrium and enhanced sampling molecular dynamics simulations. By employing window-exchange umbrella sampling, we compute free-energy profiles of activation, which show that back-to-back dimerization stabilizes a catalytically competent conformation of PKR. Key hydrophobic residues in the homodimer interface contribute to stabilization of the αC helix in an active conformation and the position of its critical glutamate residue. Using linear mutual information analysis, we analyze allosteric communication connecting the protomers' N-lobes and the αC helix dimer interface with the αC helix.
Assuntos
Simulação de Dinâmica Molecular , Conformação Proteica em alfa-Hélice , Multimerização Proteica , Termodinâmica , eIF-2 Quinase , eIF-2 Quinase/química , eIF-2 Quinase/metabolismo , Ativação Enzimática , HumanosRESUMO
AI algorithms have proven to be excellent predictors of protein structure, but whether and how much these algorithms can capture the underlying physics remains an open question. Here, we aim to test this question using the Alphafold2 (AF) algorithm: We use AF to predict the subtle structural deformation induced by single mutations, quantified by strain, and compare with experimental datasets of corresponding perturbations in folding free energy ΔΔG. Unexpectedly, we find that physical strain alone-without any additional data or computation-correlates almost as well with ΔΔG as state-of-the-art energy-based and machine-learning predictors. This indicates that the AF-predicted structures alone encode fine details about the energy landscape. In particular, the structures encode significant information on stability, enough to estimate (de-)stabilizing effects of mutations, thus paving the way for the development of novel, structure-based stability predictors for protein design and evolution.
Assuntos
Algoritmos , Dobramento de Proteína , Proteínas , Termodinâmica , Proteínas/química , Proteínas/genética , Proteínas/metabolismo , Inteligência Artificial , Mutação , Conformação ProteicaRESUMO
Thorium biosorption by a green microalga, Chlorella Vulgaris, was studied in a stirred batch reactor to investigate the effect of initial solution pH, metal ion concentration, biomass dosage, contact time, kinetics, equilibrium and thermodynamics of uptake. The green microalgae showed the highest Th adsorption capacity at 45 °C for the solution with a thorium concentration of 350 mg L-1 and initial pH of 4. The amount of uptake raised from 84 to 104 mg g-1 as the temperature increased from 15 to 45 °C for an initial metal concentration of 75 mg L-1 at pH 4. Transformation Infrared Spectroscopy (FTIR) was employed to characterize the vibrational frequency changes for peaks related to surface functional groups. Also, the scanning electron microscope (SEM) and energy-dispersive X-ray spectroscopy (EDX) were used to determine the morphological changes and elemental analysis of the biosorbent before and after the sorption process. The Langmuir isotherm was in perfect agreement with the equilibrium empirical data of thorium biosorption and the highest sorption capacity of the Chlorella Vulgaris microalgae was determined as 185.19 mg g-1. Also, the results of kinetic studies show that the thorium biosorption process follows a pseudo-second-order kinetic model. The negative value of ΔG0 indicates spontaneity and the positive values of ΔH0 indicate the endothermic nature of the adsorption process.
Assuntos
Chlorella vulgaris , Microalgas , Tório , Chlorella vulgaris/metabolismo , Tório/metabolismo , Tório/química , Adsorção , Microalgas/metabolismo , Cinética , Concentração de Íons de Hidrogênio , Biomassa , Termodinâmica , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , Água/químicaRESUMO
Fibroblast growth factor 2 (FGF2) is an attractive biomaterial for pharmaceuticals and functional cosmetics. To improve the thermo-stability of FGF2, we designed two mutants harboring four-point mutations: FGF2-M1 (D28E/C78L/C96I/S137P) and FGF2-M2 (D28E/C78I/C96I/S137P) through bioinformatics, molecular thermodynamics, and molecular modeling. The D28E mutation reduced fragmentation of the FGF2 wild type during preparation, and the substitution of a whale-specific amino acid, S137P, enhanced the thermal stability of FGF2. Surface-exposed cysteines that participate in oligomerization through intermolecular disulfide bond formation were substituted with hydrophobic residues (C78L/C78I and C96I) using the in silico method. High-resolution crystal structures revealed at the atomic level that the introduction of mutations stabilizes each local region by forming more favorable interactions with neighboring residues. In particular, P137 forms CH-π interactions with the side chain indole ring of W123, which seems to stabilize a ß-hairpin structure, containing a heparin-binding site of FGF2. Compared to the wild type, both FGF2-M1 and FGF2-M2 maintained greater solubility after a week at 45 °C, with their Tm values rising by ~ 5 °C. Furthermore, the duration for FGF2-M1 and FGF2-M2 to reach 50% residual activity at 45 °C extended to 8.8- and 8.2-fold longer, respectively, than that of the wild type. Interestingly, the hydrophobic substitution of surface-exposed cysteine in both FGF2 mutants makes them more resistant to proteolytic cleavage by trypsin, subtilisin, proteinase K, and actinase than the wild type and the Cys â Ser substitution. The hydrophobic replacements can influence protease resistance as well as oligomerization and thermal stability. It is notable that hydrophobic substitutions of surface-exposed cysteines, as well as D28E and S137P of the FGF2 mutants, were designed through various approaches with structural implications. Therefore, the engineering strategies and structural insights adopted in this study could be applied to improve the stability of other proteins.
Assuntos
Cisteína , Fator 2 de Crescimento de Fibroblastos , Interações Hidrofóbicas e Hidrofílicas , Estabilidade Proteica , Cisteína/química , Cisteína/genética , Fator 2 de Crescimento de Fibroblastos/química , Fator 2 de Crescimento de Fibroblastos/genética , Fator 2 de Crescimento de Fibroblastos/metabolismo , Mutação , Modelos Moleculares , Cristalografia por Raios X , Substituição de Aminoácidos , Humanos , TermodinâmicaRESUMO
Here we present TPPU_DSF (https://maciasnmr.net/tppu_dsf/). This is a free and open-source web application that opens, converts, fits, and calculates the thermodynamic parameters of protein unfolding from standard differential scanning fluorimetry (DSF) data in an automated manner. The software has several applications. In the context of screening compound libraries for protein binders, obtaining thermodynamic parameters provides a more robust approach to detecting hits than the changes in the melting temperature (Tm) alone, thereby helping to increase the number of positive hits in screening campaigns. Moreover, changes in ΔGuo indicate protein response to binding at lower compound concentrations than those in the Tm, thereby reducing the costs associated with the amounts of protein and compounds required for the assays. Also, by adding thermodynamic information to the Tm comparison, the software can contribute to the optimization of protein constructs and buffer conditions, a common practice before structural and functional projects.
Assuntos
Software , Termodinâmica , Proteínas/química , Internet , Desdobramento de Proteína , Fluorometria/métodos , Ligação ProteicaRESUMO
In recent years, predictive machine learning models have gained prominence across various scientific domains. However, their black-box nature necessitates establishing trust in them before accepting their predictions as accurate. One promising strategy involves employing explanation techniques that elucidate the rationale behind a model's predictions in a way that humans can understand. However, assessing the degree of human interpretability of these explanations is a nontrivial challenge. In this work, we introduce interpretation entropy as a universal solution for evaluating the human interpretability of any linear model. Using this concept and drawing inspiration from classical thermodynamics, we present Thermodynamics-inspired Explainable Representations of AI and other black-box Paradigms, a method for generating optimally human-interpretable explanations in a model-agnostic manner. We demonstrate the wide-ranging applicability of this method by explaining predictions from various black-box model architectures across diverse domains, including molecular simulations, text, and image classification.
Assuntos
Inteligência Artificial , Aprendizado de Máquina , Termodinâmica , Humanos , Entropia , AlgoritmosRESUMO
Advances in green engineering and technology have revealed a number of environmentally acceptable alternatives for water purification. In line with this, recent advances in biosorption of pollutants from aqueous solutions using animal biowaste-based activated carbon (AC) are reported herein. Apart from the fish scale-derived AC which is extensively documented, animal bones, among the rest others, have been studied most widely, followed by hair and feathers. Out of the various target water pollutants, removal of heavy metals has been mostly studied. Majority of the reports showed the Freundlich isotherm and pseudo second order as the best fit. Few investigations on the thermodynamics of the adsorption studies and reports on the Gibbs free energy change (ΔG°), enthalpy change (ΔH°), and entropy change (ΔS°) have also been discussed in this report. It has been concluded that while plant-based AC has gained wide interest, the same is not true for the animal-based counterpart albeit the latter's potential for high sorption efficiency as seen in the present report.
Assuntos
Carvão Vegetal , Poluentes Químicos da Água , Purificação da Água , Poluentes Químicos da Água/análise , Carvão Vegetal/química , Animais , Adsorção , Purificação da Água/métodos , Metais Pesados/análise , TermodinâmicaRESUMO
The integration of biochar (BC) production from organic waste with ampicillin (AMP), an emerging pollutant, adsorption is a novel and promising treatment approach. In this study, peanut shells, coffee grounds, digestates, and oyster shells were used for BC production. Among these, the use of anaerobic digestate from food waste fermentation to produce extracts for antibiotic adsorption is relatively unexplored. The pyrolysis temperature was determined using thermogravimetric analysis (TGA) and the materials were characterized with BET, SEM, FTIR, and XRD. The TGA results indicate that PSB, CRB, and DSB underwent pyrolysis involving cellulose, hemicellulose, and lignin, whereas OSB underwent crystal formation. Characterization revealed that DSB has more functional groups, a superior mesoporous structure, appropriate O/C ratio, and trace amounts of calcite crystals, which are favorable for AMP adsorption. Adsorption experiments demonstrate that all four materials adhere to the Freundlich and Langmuir isotherm and Elovich kinetic models, indicating predominant physical adsorption, with some chemical adsorption also present. Thermodynamic studies demonstrate that BC is spontaneous during adsorption and is a heat-absorbing reaction. DSB exhibits the strongest AMP adsorption. A 53.81 mg g-1 adsorbance was obtained at a dosage of 150 mg, pH = 2, and 60 °C. This study introduces innovative approaches for managing waste types and provides data to support the selection of suitable solid wastes for the preparation of BC with excellent adsorption properties. Furthermore, it lays the groundwork for future studies aimed at enhancing the AMP treatment efficacy.
Assuntos
Ampicilina , Carvão Vegetal , Carvão Vegetal/química , Adsorção , Ampicilina/química , Antibacterianos/química , Resíduos Sólidos , Cinética , Termodinâmica , Pirólise , TermogravimetriaRESUMO
In order for computer-aided drug design to fulfil its long held promise of delivering new medicines faster and cheaper, extensive development and validation work must be done first. This pertains particularly to molecular dynamics force fields where one important aspect-the hydration free energy (HFE) of small molecules-is often insufficiently analyzed. While most benchmarking studies report excellent accuracies of calculated hydration free energies-usually within 2 kcal/mol of experimental values-we find that deeper analysis reveals significant shortcomings. Herein, we report a dependence of HFE prediction errors on ligand molecular weight-the higher the weight, the bigger the prediction error and the higher the probability the calculated result is erroneous by a large amount. We show that in the drug-like molecular weight region, HFE predictions can easily be off by 5 kcal/mol or more. This is likely to be highly problematic in a drug discovery and development setting. We make our HFE results and molecular descriptors freely and fully available in order to encourage deeper analysis of future molecular dynamics results and facilitate development of the next generation of force fields.
Assuntos
Simulação de Dinâmica Molecular , Peso Molecular , Termodinâmica , Água , Água/química , Ligantes , Desenho de FármacosRESUMO
This study focused on investigating thermal degradation behaviors, kinetics, reaction mechanisms, synergistic effects, and thermodynamic parameters of wood sawdust (WSD), linear low-density polyethylene (LLDPE), and their blends (LW1:3, LW1:1, and LW3:1) during co-pyrolysis in a thermogravimetric analyzer (TGA). Thermal behavior exhibited a LW1:3 blend (25 wt.% LLDPE) showing significant mass loss at lower temperatures (150 to 300 °C) compared to the individual feedstocks, such as 150 to 400 °C and 300 to 520 °C for WSD and LLDPE, respectively. The iso-conversional methods (KAS, FWO, and FM) were used to determine the kinetic parameters (Ea and A), and the activation energy drop was highest for the LW1:3 blend. According to the master plots, the third-order reaction (O3), nucleation (P2/3), and diffusional model (D4) were the predominant reaction mechanisms for the co-pyrolysis of the LW1:3, LW1:1, and LW3:1 blend, respectively. The thermodynamic parameters demonstrate that a small amount of plastic addition into WSD can improve the reactivity of the blend, shorten the reaction time, and cause less energy-intensive reactions. The values of ΔH, ΔG, and ΔS also confirmed the co-pyrolysis process's spontaneity and endothermic nature. The Fourier transforms infrared spectrometer (FTIR) spectra of raw feedstock, blends, and their biochar revealed some of the peaks were shifted, the intensity was reduced, and disappearance can happen when the temperature was increased. Using the experimental and theoretical/predicted activation energies, the parity chart illustrates the synergistic effects of co-pyrolysis of different blends, and the LW1:3 blend has a favorable synergistic impact. These results could be helpful in process optimization and designing an effective reactor system for co-pyrolysis.
Assuntos
Polietileno , Pirólise , Termodinâmica , Termogravimetria , Madeira , Madeira/química , Cinética , Polietileno/químicaRESUMO
Cell surface signaling (CSS) is a means of rapidly adjusting transcription in response to extracellular stimuli in Gram-negative bacteria. The pseudobactin BN7/8 uptake (Pup) system not only imports iron but also upregulates its own transcription through CSS in Pseudomonas capeferrum. In the absence of ferric pseudobactin BN7/8, the signaling components are maintained in a resting state via the formation of a periplasmic complex between the N-terminal signaling domain (NTSD) of the outer membrane iron-transporter, PupB, and the C-terminal CSS domain (CCSSD) of the sigma regulator, PupR. The previously determined 1.6 Å crystal structure of this periplasmic complex has allowed us to probe the structural and thermodynamic consequences of mutating key interfacial residues. In this report, we describe the solution structure of the PupB NTSD and use Nuclear Magnetic Resonance spectroscopy, Isothermal Titration Calorimetry, and Circular Dichroism spectroscopy together with thermal denaturation to investigate whether three PupB point mutations, Q69K, H72D, and L74A, influence the interaction merely due to the chemical nature of the amino acid substitution or also cause changes in overall protein structure. Our results demonstrate that binding to the PupR CCSSD does not alter the structure of PupB NTSD and that the individual mutations have only minor effects on structure. The mutations generally lower thermodynamic stability of the NTSD and weaken binding to the CCSSD. These findings validate the X-ray crystal structure interface, emphasizing the importance of amino acid chemical nature at the interface.
Assuntos
Proteínas de Bactérias , Pseudomonas , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Pseudomonas/metabolismo , Pseudomonas/genética , Domínios Proteicos , Transdução de Sinais , Termodinâmica , Modelos MolecularesRESUMO
Lipid rafts are nanoscopic assemblies of sphingolipids, cholesterol, and specific membrane proteins. They are believed to underlie the experimentally observed lateral heterogeneity of eukaryotic plasma membranes and implicated in many cellular processes, such as signaling and trafficking. Ternary model membranes consisting of saturated lipids, unsaturated lipids, and cholesterol are common proxies because they exhibit phase coexistence between a liquid-ordered (lo) and liquid-disordered (ld) phase and an associated critical point. However, plasma membranes are also asymmetric in terms of lipid type, lipid abundance, leaflet tension, and corresponding cholesterol distribution, suggesting that rafts cannot be examined separately from questions about elasticity, curvature torques, and internal mechanical stresses. Unfortunately, it is challenging to capture this wide range of physical phenomenology in a single model that can access sufficiently long length- and time scales. Here we extend the highly coarse-grained Cooke model for lipids, which has been extensively characterized on the curvature-elastic front, to also represent raft-like lo/ld mixing thermodynamics. In particular, we capture the shape and tie lines of a coexistence region that narrows upon cholesterol addition, terminates at a critical point, and has coexisting phases that reflect key differences in membrane order and lipid packing. We furthermore examine elasticity and lipid diffusion for both phase separated and pure systems and how they change upon the addition of cholesterol. We anticipate that this model will enable significant insight into lo/ld phase separation and the associated question of lipid rafts for membranes that have compositionally distinct leaflets that are likely under differential stress-like the plasma membrane.
Assuntos
Colesterol , Microdomínios da Membrana , Microdomínios da Membrana/química , Colesterol/química , Elasticidade , TermodinâmicaRESUMO
Mercury (Hg) is a hazardous heavy metal, non-biodegradable and toxic, posing a serious threat to aquatic life and human health. Therefore, the removal of Hg ions from contaminated water using effective and eco-friendly adsorbents is necessary. In the present study, three magnetic chitosan-based organic-inorganic nanocomposites, such as CS-MnFe2O4, CS-MnFe2O4-CoS, and CS-MnFe2O4-CoS-MWCNTs, were designed and constructed to investigate their capacity for adsorbing Hg ions from aqueous solutions. The physicochemical properties of prepared composites were characterized by various analyses. The BET analyses indicated their high surface area and porous structure, and the N2 adsorption-desorption showed that the modification of CS in three stages by MnFe2O4 and crosslinking reaction, CoS preparation, and MWCNT incorporation resulted in increased N2 adsorption. The XRD confirms the synthesis of MnFe2O4 and CoS in the CS matrix and also the distinct peaks of MWCNTs. The CS-MnFe2O4-CoS-MWCNTs showed acceptable thermal stability with 45% char yields and superparamagnetic properties with magnetic saturation (Ms) of 16 emu g-1. The interactive impacts of independent variables (pH, contact time, and adsorbent dosage) on the removal percentage of Hg(II) onto three prepared adsorbents, as well as the process optimization, were assessed by the Box-Behnken design. The optimum conditions were identified, and the data from the analysis of variance showed that the three independent factors (pH, contact time, and adsorbent dosage) significantly influenced the adsorption of Hg(II). The adsorption isotherm and thermodynamics analysis investigation showed that at low concentrations of Hg(II), the adsorption process was both endothermic and spontaneous for the studied adsorbents.
Assuntos
Quitosana , Compostos Férricos , Compostos de Manganês , Mercúrio , Termodinâmica , Poluentes Químicos da Água , Mercúrio/química , Poluentes Químicos da Água/química , Poluentes Químicos da Água/análise , Adsorção , Quitosana/química , Cinética , Compostos Férricos/química , Compostos de Manganês/química , Nanotubos de Carbono/química , Recuperação e Remediação Ambiental/métodos , Purificação da Água/métodosRESUMO
The cell membrane, also called the plasma membrane, is the membrane on the cytoplasmic surface that separates the extracellular from the intracellular. It is thin, about 10 nm thick when viewed with an electron microscope, and is composed of two monolayers of phospholipid membranes (lipid bilayers) containing many types of proteins. It is now known that this cell membrane not only separates the extracellular from the intracellular, but is also involved in sensory stimuli such as pain, itching, sedation, and excitement. Since the "Fluid mosaic model" was proposed for cell membranes, molecules have been thought to be homogeneously distributed on the membrane surface. Later, at the end of the twentieth century, the existence of "Phase-separated microdomain structures" consisting of ordered phases rich in saturated lipids and cholesterol was suggested, and these were termed "Lipid rafts." A model in which lipid rafts regulate cell signaling has been proposed and is the subject of active research.This chapter first outlines the physicochemical properties and thermodynamic models of membrane phase separation (lipid rafts), which play an important role in cell signaling. Next, how physiologically active molecules such as local anesthetics, cooling agents (menthol), and warming agents (capsaicin) interact with artificial cell membranes will be presented.It is undeniable that the plasma membrane contains many channels and receptors that are involved in the propagation of sensory stimuli. At the same time, however, it is important to understand that the membrane exerts a significant influence on the intensity and propagation of these stimuli.
Assuntos
Microdomínios da Membrana , Microdomínios da Membrana/metabolismo , Microdomínios da Membrana/química , Humanos , Animais , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , Transdução de Sinais , Materiais Biomiméticos/química , Materiais Biomiméticos/metabolismo , Termodinâmica , Membrana Celular/metabolismo , Membrana Celular/química , Biomimética/métodos , Colesterol/química , Colesterol/metabolismoRESUMO
Utilizing molecular dynamics and free energy perturbation, we examine the relative binding affinity of several covalent polycyclic aromatic hydrocarbon - DNA (PAH-DNA) adducts at the central adenine of NRAS codon-61, a mutational hotspot implicated in cancer risk. Several PAHs classified by the International Agency for Research on Cancer as probable, possible, or unclassifiable as to carcinogenicity are found to have greater binding affinity than the known carcinogen, benzo[a]pyrene (B[a]P). van der Waals interactions between the intercalated PAH and neighboring nucleobases, and minimal disruption of the DNA duplex drive increases in binding affinity. PAH-DNA adducts may be repaired by global genomic nucleotide excision repair (GG-NER), hence we also compute relative free energies of complexation of PAH-DNA adducts with RAD4-RAD23 (the yeast ortholog of human XPC-RAD23) which constitutes the recognition step in GG-NER. PAH-DNA adducts exhibiting the greatest DNA binding affinity also exhibit the least RAD4-RAD23 complexation affinity and are thus predicted to resist the GG-NER machinery, contributing to their genotoxic potential. In particular, the fjord region PAHs dibenzo[a,l]pyrene, benzo[g]chrysene, and benzo[c]phenanthrene are found to have greater binding affinity while having weaker RAD4-RAD23 complexation affinity than their respective bay region analogs B[a]P, chrysene, and phenanthrene. We also find that the bay region PAHs dibenzo[a,j]anthracene, dibenzo[a,c]anthracene, and dibenzo[a,h]anthracene exhibit greater binding affinity and weaker RAD4-RAD23 complexation affinity than B[a]P. Thus, the study of PAH genotoxicity likely needs to be substantially broadened, with implications for public policy and the health sciences. This approach can be broadly applied to assess factors contributing to the genotoxicity of other unclassified compounds.
Assuntos
Adutos de DNA , Hidrocarbonetos Policíclicos Aromáticos , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/química , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Adutos de DNA/química , Adutos de DNA/metabolismo , Adutos de DNA/genética , Humanos , Reparo do DNA , Mutagênicos/toxicidade , Mutagênicos/química , Simulação de Dinâmica Molecular , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/química , Termodinâmica , Benzo(a)pireno/toxicidade , Benzo(a)pireno/química , Benzo(a)pireno/metabolismo , DNA/química , DNA/metabolismo , Benzopirenos/toxicidade , Benzopirenos/química , Benzopirenos/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/químicaRESUMO
With the increasing incidence of chronic kidney disease, the effective control of protein-bound uremic toxins (PBUTs), which are difficult to remove through dialysis, has become a priority. In this study, the adsorption and diffusion behaviors of several metal-organic frameworks (MOFs) for PBUTs (indoxyl sulfate and p-cresyl sulfate) were studied by molecular dynamics (MD) simulations and umbrella sampling. For the NU series of MOFs, good correlations between the Gibbs free energy (ΔG) and the experimental clearance rates of PBUTs are found. For the adsorption behaviors, in terms of ΔG, DAJWET exhibits the best adsorption effect for indoxyl sulfate (IS), whereas NU-1000 shows the best effect for p-cresyl sulfate (pCS). Similar trends observed in the radial distribution function and mean square displacement results suggest that the π-π stacking interactions play a crucial role in the adsorption and diffusion of PBUTs by MOFs. Furthermore, it can be concluded that MOFs with highly conjugated groups (porphyrin rings and pyrene groups) tend to generate more PBUT attraction, and provide design principles for potential MOF candidates in the removal of PBUTs.