Search results for "imulation"
showing 10 items of 7271 documents
Exploring Strategies for Labeling Viruses with Gold Nanoclusters through Non-equilibrium Molecular Dynamics Simulations.
2017
Biocompatible gold nanoclusters can be utilized as contrast agents in virus imaging. The labeling of viruses can be achieved noncovalently but site-specifically by linking the cluster to the hydrophobic pocket of a virus via a lipid-like pocket factor. We have estimated the binding affinities of three different pocket factors of echovirus 1 (EV1) in molecular dynamics simulations combined with non-equilibrium free-energy calculations. We have also studied the effects on binding affinities with a pocket factor linked to the Au102pMBA44 nanocluster in different protonation states. Although the absolute binding affinities are over-estimated for all the systems, the trend is in agreement with r…
Interactions of human P-glycoprotein transport substrates and inhibitors at the drug binding domain: Functional and molecular docking analyses
2015
Rhodamine 123 (R123) transport substrate sensitizes P-glycoprotein (P-gp) to inhibition by compound 2c (cis-cis) N,N-bis(cyclohexanolamine)aryl ester isomer in a concentration-dependent manner in human MDR1-gene transfected mouse T-lymphoma L5178 cells as shown previously. By contrast, epirubicin (EPI) concentration changes left unaltered 2c IC50 values of EPI efflux. To clarify this discrepancy, defined molecular docking (DMD) analyses of 12 N,N-bis(cyclohexanolamine)aryl esters, the highly flexible aryl ester analog 4, and several P-gp substrate/non-substrate inhibitors were performed on human P-gp drug- or nucleotide-binding domains (DBD or NBD). DMD measurements yielded lowest binding e…
Fluorinated Chaperone−β-Cyclodextrin Formulations for β-Glucocerebrosidase Activity Enhancement in Neuronopathic Gaucher Disease
2017
Amphiphilic glycomimetics encompassing a rigid, undistortable nor-tropane skeleton based on 1,6-anhydro-L-idonojirimycin and a polyfluorinated antenna, when formulated as the corresponding inclusion complexes with β-cyclodextrin (βCD), have been shown to behave as pharmacological chaperones (PCs) that efficiently rescue lysosomal β- glucocerebrosidase mutants associated to the neuronopathic variants of Gaucher disease (GD), including the highly refractory L444P/L444P and L444P/P415R single nucleotide polymorphs, in patient fibroblasts. The body of work here presented includes the design criteria for the PC prototype, the synthesis of a series of candidates, the characterization of the PC:βC…
Screening of potent phytochemical inhibitors against SARS-CoV-2 protease and its two Asian mutants
2021
Abstract Background COVID-19, declared a pandemic in March 2020 by the World Health Organization is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The virus has already killed more than 2.3 million people worldwide. Object The principal intent of this work was to investigate lead compounds by screening natural product library (NPASS) for possible treatment of COVID-19. Methods Pharmacophore features were used to screen a large database to get a small dataset for structure-based virtual screening of natural product compounds. In the structure-based screening, molecular docking was performed to find a potent inhibitor molecule against the main protease (Mpro) of SARS-…
Balanced Bcl-3 expression in murine CD4+T cells is required for generation of encephalitogenic Th17 cells
2017
The function of NF-κB family members is controlled by multiple mechanisms including the transcriptional regulator Bcl-3, an atypical member of the IκB family. By using a murine model of conditional Bcl-3 overexpression specifically in T cells, we observed impairment in the development of Th2, Th1 and Th17 cells. High expression of Bcl-3 promoted CD4+ T-cell survival, but at the same time suppressed proliferation in response to TCR stimulation, resulting in reduced CD4+ T-cell expansion. As a consequence, T cell specific overexpression of Bcl-3 led to reduced inflammation in the small intestine of mice applied with anti-CD3 in a model of gut inflammation. Moreover, impaired Th17-cell develop…
Neurons in the pigeon caudolateral nidopallium differentiate Pavlovian conditioned stimuli but not their associated reward value in a sign-tracking p…
2016
AbstractAnimals exploit visual information to identify objects, form stimulus-reward associations, and prepare appropriate behavioral responses. The nidopallium caudolaterale (NCL), an associative region of the avian endbrain, contains neurons exhibiting prominent response modulation during presentation of reward-predicting visual stimuli, but it is unclear whether neural activity represents valuation signals, stimulus properties, or sensorimotor contingencies. To test the hypothesis that NCL neurons represent stimulus value, we subjected pigeons to a Pavlovian sign-tracking paradigm in which visual cues predicted rewards differing in magnitude (large vs. small) and delay to presentation (s…
Identification of control targets in Boolean molecular network models via computational algebra
2015
Motivation: Many problems in biomedicine and other areas of the life sciences can be characterized as control problems, with the goal of finding strategies to change a disease or otherwise undesirable state of a biological system into another, more desirable, state through an intervention, such as a drug or other therapeutic treatment. The identification of such strategies is typically based on a mathematical model of the process to be altered through targeted control inputs. This paper focuses on processes at the molecular level that determine the state of an individual cell, involving signaling or gene regulation. The mathematical model type considered is that of Boolean networks. The pot…
Reorganization of platelet membrane sphingomyelins by adenosine diphosphate and ticagrelor
2018
IF 2.766 (2017); International audience; Platelets are major targets for the treatment of thrombo-embolic disorders. Their plasma membrane contains specialized microdomains enriched in sphingomyelins and free cholesterol including membrane receptors. P2Y12 receptors need to be situated in these domains to be able to conduct activation signaling by adenosine diphosphate (ADP). We studied the impact of ticagrelor, a P2Y12 antagonist, and ADP on the composition and distribution of sphingomyelins in detergent-resistant membrane (DRM) of platelet membranes. Platelets were obtained from healthy donors. DRMs of platelet membranes were isolated in 4 experimental groups: control; ADP, with platelets…
2-methoxyestradiol impacts on amino acids-mediated metabolic reprogramming in osteosarcoma cells by interaction with NMDA receptor
2017
Deregulation of serine and glycine metabolism, have been identified to function as metabolic regulators in supporting tumor cell growth. The role of serine and glycine in regulation of cancer cell proliferation is complicated, dependent on concentrations of amino acids and tissue-specific. D-serine and glycine are coagonists of N-methyl-D-aspartate receptor subunit GRIN1. Importantly, NMDA receptors are widely expressed in cancer cells and play an important role in regulation of cell death, proliferation and metabolism of numerous malignancies. The aim of the present work was to associate the metabolism of glycine and D-serine with the anticancer activity of 2-methoxyestradiol. 2-methoxyest…
Neural oscillations in the infralimbic cortex after electrical stimulation of the amygdala. Relevance to acute stress processing
2017
The stress system coordinates the adaptive reactions of the organism to stressors. Therefore, dysfunctions in this circuit may correlate to anxiety-related disorders, including depression. Comprehending the dynamics of this network may lead to a better understanding of the mechanisms that underlie these diseases. The central nucleus of the amygdala (CeA) activates the hypothalamic–pituitary–adrenal axis and brainstem nodes by triggering endocrine, autonomic and behavioral stress responses. The medial prefrontal cortex plays a significant role in regulating reactions to stressors, and is specifically important for limiting fear responses. Brain oscillations reflect neural systems activity. S…