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Essential oils (EOs) are natural products currently used to control arthropods, and their interaction with insect odorant-binding proteins (OBPs) is fundamental for the discovery of new repellents. This in silico study aimed to predict the potential of EO components to interact with odorant proteins. A total of 684 EO components from PubChem were docked against 23 odorant binding proteins from Protein Data Bank using AutoDock Vina. The ligands and proteins were optimized using Gaussian 09 and Sybyl-X 2.0, respectively. The nature of the protein-ligand interactions was characterized using LigandScout 4.0, and visualization of the binding mode in selected complexes was carried out by Pymol. Additionally, complexes with the best binding energy in molecular docking were subjected to 500 ns molecular dynamics simulations using Gromacs. The best binding affinity values were obtained for the 1DQE-ferutidine (-11 kcal/mol) and 2WCH-kaurene (-11.2 kcal/mol) complexes. Both are natural ligands that dock onto those proteins at the same binding site as DEET, a well-known insect repellent. This study identifies kaurene and ferutidine as possible candidates for natural insect repellents, offering a potential alternative to synthetic chemicals like DEET.
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Simulação de Acoplamento Molecular , Óleos Voláteis , Receptores Odorantes , Receptores Odorantes/química , Receptores Odorantes/metabolismo , Óleos Voláteis/química , Animais , Proteínas de Insetos/química , Proteínas de Insetos/metabolismo , Simulação de Dinâmica Molecular , Repelentes de Insetos/química , Ligantes , Relação Quantitativa Estrutura-AtividadeRESUMO
In this theoretical investigation, we delve into the significant effects of donor impurity position within core/shell quantum dot structures: type I (CdTe/ZnS) and type II (CdTe/CdS). The donor impurity's precise location within both the core and the shell regions is explored to unveil its profound influence on the electronic properties of these nanostructures. Our study investigates the diamagnetic susceptibility and binding energy of the donor impurity while considering the presence of an external magnetic field. Moreover, the lattice mismatch-induced strain between the core and shell materials is carefully examined as it profoundly influences the electronic structure of the quantum dot system. Through detailed calculations, we analyze the strain effects on the conduction and valence bands, as well as the electron and hole energy spectrum within the core/shell quantum dots. The results highlight the significance of donor impurity position as a key factor in shaping the behaviors of impurity binding energy and diamagnetic susceptibility. Furthermore, our findings shed light on the potential for tuning the electronic properties of core/shell quantum dots through precise impurity positioning and strain engineering.
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We calculate energies of shallow donors confined in a rolled-up quantum well in the presence of the electric field by solving numerically the Schrödinger equation in natural curvilinear coordinates. It is found that the curves of density of states (DOSs) are very sensitive to the variation of the donor position, the geometry of the spiral and the applied electric field value. Novel results for dependencies of donor's dipole moment and its polarizability on the electric field strength and its orientation, for different donor positions are presented. Additionally, we found that the anisotropic Stark effect of the first order provides in this structure a dependency of the polarizability on the external electric field in a spike-like shape, giving rise to a sharp variation of the dipole moment.
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The pineal melatonin (N-acetyl-5-methoxytryptamine) is a molecule associated in a way or another with probably all physiological systems, aiming to fulfil its functional integrative roles in central nervous system activity, sleep and wakefulness cycles, energy metabolism and thermoregulation, immune, reproductive, endocrine, cardiovascular, respiratory and excretory systems. Within this context, the present study aimed to assess in silico the formation of complexes between ligand melatonin and other potential receptor proteins by molecular docking analyses. The main steps established in this experimental procedure were: a) search and selection of the 3D structure of the melatonin from DrugBank; b) search and selection of 3D structures of other target receptor proteins using STRING, protein BLAST and database PDB; and c) formation of the complexes between melatonin and receptors selected using AutoDock4.0 server by molecular docking analyses. High reliability score and significant similarity were only identified between type 1B melatonin and alpha-2A adrenergic receptor. Thus, molecular docking assays were carried out using ligand melatonin and crystallographic structures of the alpha-2A adrenergic receptor coupled to an antagonist (ID PDB 6kux) and a partial agonist (ID PDB 6kuy) available in the database PDB. Binding energy values of -6.79 and -6.98 kcal/mol and structural stability by non-covalent intermolecular interactions were predicted during the formation of complexes between melatonin and alpha-2A adrenergic receptor 6kux and 6kuy, respectively. In this way, the findings described in current study may indicate strong interactions between melatonin and adrenoceptors, suggesting its possible partial agonist effect on the activation of the alfa-2A adrenergic receptor.(AU)
A melatonina pineal (N-acetil-5-metoxitriptamina) é uma molécula associada de um modo ou outro com provavelmente todos os sistemas fisiológicos, visando cumprir seus papéis funcionais integradores na atividade do sistema nervoso central, ciclos de sono e vigília, metabolismo energético e termorregulação, sistemas imunológico, reprodutivo, endócrino, cardiovascular, respiratório e excretor. Assim, o presente estudo objetivou avaliar in silico a formação de complexos entre o ligante melatonina e outras proteínas potenciais receptoras por meio de análises de docagem molecular. As principais etapas estabelecidas neste procedimento experimental foram: a) busca e seleção da estrutura 3D da melatonina a partir do banco de dados DrugBank; b) busca e seleção de estruturas 3D de outras proteínas receptoras-alvo utilizando STRING, proteína BLAST e o banco de dados PDB; e c) avaliação da formação dos complexos entre melatonina e receptores selecionados a partir do servidor AutoDock4.0 para análises de docagem molecular. Alto escore de confiabilidade e similaridade significativa foram identificados apenas entre a melatonina do tipo 1B e o receptor alfa-2A adrenérgico. Valores de energia de ligação de -6,79 e -6,98 kcal/mol e estabilidade estrutural pela presença de interações intermoleculares não covalentes foram preditos durante a formação de complexos entre o ligante melatonina e os receptores adrenérgico alfa-2A 6kux e 6kuy, respectivamente. Dessa forma, os achados descritos no presente estudo podem indicar fortes interações entre melatonina e adrenoceptores, sugerindo seu possível efeito agonista parcial na ativação do receptor alfa-2A adrenérgico.(AU)
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Humanos , Sono , Vigília , Sistema Nervoso Central/fisiologia , Melatonina/fisiologia , Simulação de Acoplamento MolecularRESUMO
Experimentally estimating peptide-major histocompatibility complex (pMHC) binding affinity has been quite challenging due to the many receptors and the many potential ligands implicated in it. We have thus proposed a straightforward computational methodology considering the different mechanisms involved in pMHC binding to facilitate studying such receptor-ligand interactions. We have developed a pipeline using semi-empirical quantum mechanical methods for calculating pMHC class I and II molecules' binding energy (BE). This pipeline can systematize the methodology for calculating pMHC system BE, enabling the rational design of T-cell epitopes to be used as pharmaceuticals and vaccines.
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Biologia Computacional/métodos , Antígenos de Histocompatibilidade/química , Modelos Moleculares , Oligopeptídeos/química , Teoria Quântica , Software , Algoritmos , Sequência de Aminoácidos , Antígenos de Histocompatibilidade/imunologia , Antígenos de Histocompatibilidade/metabolismo , Humanos , Ligantes , Oligopeptídeos/imunologia , Oligopeptídeos/metabolismo , Ligação Proteica , Relação Estrutura-AtividadeRESUMO
BACKGROUND: Anticarsia gemmatalis larvae are key defoliating pests of soybean plants. Inorganic insecticides, harmful to the environment and human health, are the main molecules used in the control of this pest. To apply more sustainable management methods, organic molecules with high specificities, such as proteinaceous protease inhibitors, have been sought. Thus, molecular docking studies, kinetics assays, and biological tests were performed to evaluate the inhibitory activity of two peptides (GORE1 and GORE2) rationally designed to inhibit trypsin-like enzymes, which are the main proteases of A. gemmatalis midgut. RESULTS: The molecular docking simulations revealed critical hydrogen bonding patterns of the peptides with key active site residues of trypsin-like proteases of A. gemmatalis and other Lepidopteran insects. The negative values of binding energy indicate that hydrogen bonds potentiate the tight binding of the peptides with trypsin-like proteases, predicting an effective inhibition. The inhibition's rate constants (Ki) were 0.49 and 0.10 mM for GORE1 and GORE2, resulting in effective inhibition of the activity trypsin on the L-BApNA substrate in the in vitro tests, indicating that the peptide GORE2 has higher inhibitory capacity on the A. gemmatalis trypsins. In addition, the two peptides were determined to be reversible competitive inhibitors. The in vivo test demonstrated that the peptides harm the survival and development of A. gemmatalis larvae. CONCLUSION: These results suggest that these peptides are potential candidates in the management of A. gemmatalis larvae and provide baseline information for the design of new trypsin-like inhibitors based on peptidomimetic tools. © 2020 Society of Chemical Industry.
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Microbioma Gastrointestinal , Lepidópteros , Mariposas , Animais , Humanos , Larva , Simulação de Acoplamento Molecular , Peptídeo Hidrolases , Peptídeos , TripsinaRESUMO
Biofilms are communities of microorganisms that can colonize biotic and abiotic surfaces and thus play a significant role in the persistence of bacterial infection and resistance to antimicrobial. About 65% and 80% of microbial and chronic infections are associated with biofilm formation, respectively. The increase in infections by multi-resistant bacteria instigates the need for the discovery of novel natural-based drugs that act as inhibitory molecules. The inhibition of diguanylate cyclases (DGCs), the enzyme implicated in the synthesis of the second messenger, cyclic diguanylate (c-di-GMP), involved in the biofilm formation, represents a potential approach for preventing the biofilm development. It has been extensively studied using PleD protein as a model of DGC for in silico studies as virtual screening and as a model for in vitro studies in biofilms formation. This study aimed to search for natural products capable of inhibiting the Caulobacter crescentus enzyme PleD. For this purpose, 224,205 molecules from the natural products ZINC15 database, have been evaluated through molecular docking and molecular dynamic simulation. Our results suggest trans-Aconitic acid (TAA) as a possible starting point for hit-to-lead methodologies to obtain new inhibitors of the PleD protein and hence blocking the biofilm formation.
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Anti-Infecciosos/farmacologia , Biofilmes/crescimento & desenvolvimento , Produtos Biológicos/farmacologia , Anti-Infecciosos/química , Proteínas de Bactérias/química , Biofilmes/efeitos dos fármacos , Ligação de Hidrogênio , Ligantes , Testes de Sensibilidade Microbiana , Simulação de Dinâmica Molecular , TermodinâmicaRESUMO
From a medical point of view lot of existing antibiotics became unusable because microbial gained strong antibiotic resistance. The combination of two compounds in one core may lead to kill such type of pathogens. Herein, we developed pyranopyrazole derivatives comprising benzoxazole moiety by green approach strategy and studied their antimicrobial performance on four bacteria and two fungi. As a result, most of the compounds delivered reliable toxicity to kill the pathogens. In those,6aexhibited considerable activity against the microbial pathogens. Moreover,compounds 6d, 6l,and6nshowed prominent antibacterial activity. In addition, molecular docking studies of docked compounds revealed the strong bonding interaction with DNA-Gyrase and were docked into the intercalation location of DNA of the DNA-gyrase complex. The molecule bounded to the DNA stabilized by the H bonds, hydrophobic interactions, and π-π interaction. In addition, the linked 5-chlorobenazoxazole structure stabilized by the DT-8 and DG2009 of the F chain with pi-pi interactions. From the computer-aided results, it was observed that compound6a demonstrated maximum docking score -10.0 kcal/mole towards DNA-gyrase. Overall, this investigation suggested that these biologically active compounds can be utilized as leads for preclinical studies with the goal of developing newer antimicrobial drugs.
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Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Benzoxazóis/química , Benzoxazóis/farmacologia , Pirazóis/química , Pirazóis/farmacologia , Anti-Infecciosos/síntese química , Bactérias/efeitos dos fármacos , Bactérias/enzimologia , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Benzoxazóis/síntese química , DNA Girase/metabolismo , Desenho de Fármacos , Farmacorresistência Bacteriana , Farmacorresistência Fúngica , Fungos/efeitos dos fármacos , Fungos/enzimologia , Química Verde , Humanos , Simulação de Acoplamento Molecular , Micoses/tratamento farmacológico , Micoses/microbiologia , Pirazóis/síntese química , Inibidores da Topoisomerase II/síntese química , Inibidores da Topoisomerase II/química , Inibidores da Topoisomerase II/farmacologiaRESUMO
The properties of the conduction band energy states of an electron interacting with a donor impurity center in spherical sector-shaped GaAs-Al0.3Ga0.7As quantum dots are theoretically investigated. The study is performed within the framework of the effective mass approximation through the numerical solution of the 3D Schrödinger equation for the envelope function via the finite element method. The modifications undergone by the spectrum due to the changes in the conical structure geometry (radius and apical angle) as well as in the position of the donor atom are discussed. With the information regarding electron states the linear optical absorption coefficient associated with transition between confined energy levels is evaluated and its features are discussed. The comparison of results obtained within the considered model with available experimental data in GaAs truncated-whisker-like quantum dots shows very good agreement. Besides, our simulation leads to identify the lowest energy photoluminescence peak as donor-related, instead of being associated to acceptor atoms, as claimed after experimental measurement (Hiruma et al. (1995) [14]). Also, a checking of our numerical approach is performed by comparing with analytical solutions to the problem of a spherical cone-shaped GaN with infinite confinement and donor impurity located at the cone apex. Coincidence is found to be remarkable.
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A series of 44 hybrid compounds that included in their structure tetrahydroquinoline (THQ) and isoxazole/isoxazoline moieties were synthesized through the 1,3-dipolar cycloaddition reaction (1,3-DC) from the corresponding N-allyl/propargyl THQs, previously obtained via cationic Povarov reaction. In vitro cholinergic enzymes inhibition potential of all compounds was tested. Enzyme inhibition assays showed that some hybrids exhibited significant potency to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Especially, the hybrid compound 5n presented the more effective inhibition against AChE (4.24 µM) with an acceptable selectivity index versus BChE (SI: 5.19), while compound 6aa exhibited the greatest inhibition activity on BChE (3.97 µM) and a significant selectivity index against AChE (SI: 0.04). Kinetic studies were carried out for compounds with greater inhibitory activity of cholinesterases. Structure-activity relationships of the molecular hybrids were analyzed, through computational models using a molecular cross-docking algorithm and Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) binding free energy approach, which indicated a good correlation between the experimental inhibition values and the predicted free binding energy.
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Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Isoxazóis/química , Quinolinas/química , Acetilcolinesterase/química , Sítios de Ligação , Domínio Catalítico , Técnicas de Química Sintética , Inibidores da Colinesterase/síntese química , Ativação Enzimática/efeitos dos fármacos , Humanos , Ligação de Hidrogênio , Cinética , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Ligação Proteica , Relação Estrutura-AtividadeRESUMO
An investigation of the energetics of small lithium clusters doped either with a hydrogen or with a fluorine atom as a function of the number of lithium atoms using fixed-node diffusion quantum Monte Carlo (DMC) simulation is reported. It is found that the binding energy (BE) for the doped clusters increases in absolute values leading to a more stable system than for the pure ones in excellent agreement with available experimental measurements. The BE increases for pure, remains almost constant for hydrogenated, and decreases rapidly toward the bulk lithium for the fluoride as a function of the number of lithium atoms in the clusters. The BE, dissociation energy as well as the second difference in energy display a pronounced odd-even oscillation with the number of lithium atoms. The electron correlation inverts the odd-even oscillation pattern for the doped in comparison with the pure clusters and has an impact of 29%-83% to the BE being higher in the pure cluster followed by the hydrogenated and then by the fluoride. The dissociation energy and the second difference in energy indicate that the doped cluster Li3 H is the most stable whereas among the pure ones the more stable are Li2 , Li4 , and Li6 . The electron correlation energy is crucial for the stabilization of Li3 H. © 2016 Wiley Periodicals, Inc.
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Three-dimensional models of the alpha- and beta-1 subunits of the calcium-activated potassium channel (BK) were predicted by threading modeling. A recursive approach comprising of sequence alignment and model building based on three templates was used to build these models, with the refinement of non-conserved regions carried out using threading techniques. The complex formed by the subunits was studied by means of docking techniques, using 3D models of the two subunits, and an approach based on rigid-body structures. Structural effects of the complex were analyzed with respect to hydrogen-bond interactions and binding-energy calculations. Potential interaction sites of the complex were determined by referencing a study of the difference accessible surface area (DASA) of the protein subunits in the complex.
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The quantum modeling interaction properties of fluorouracil radicals on the single walled carbon nanotubes surface is researched via MNDO/d calculations. We have studied the effect of diameter, length, position and rotational characteristics of CNT on binding fluorouracil. Our results suggest that the binding energy is lower as the CNT diameter increases, while as the CNT length increases the binding energy initially increases and then slightly increases.
Las propiedades de interacción, según el modelo cuántico, de los radicales de flourouracil ubicados en la superficie de los nanotubos de carbono de pared simple se investigan a través de cálculos MNDO/d. Hemos estudiado el efecto del diámetro, la longitud, la posición y las características rotacionales de CNT en la síntesis de fruorouracil. Nuestros resultados sugieren que la energía de síntesis baja en la medida en que aumenta el diámetro, mientras que a medida que aumenta la longitud, la energía de síntesis inicialmente disminuye y luego aumenta levemente.
As propriedades da interação, segundo o modelo quântico, do radicais de flourouracil localizados na superfície de nanotubos de carbono com paredes simples são pesquiçadas a traverso de cálculos MNDO/d. Estudamos o efeito do diâmetro, comprimento, posição e características rotacionais do CNT na síntese de fruorouracil. Nossos resultados sugerem que a energia de síntese baixa à medida que aumenta o diâmetro, enquanto que à medida que o comprimento aumenta, a energia de síntese inicialmente diminui e depois aumenta um pouco.