Receptor-interacting protein kinase 2 (RIPK2) plays an essential role in autoimmune response and is suggested as a target for inflammatory diseases. A pharmacophore model was built from a dataset with ponatinib (template) and 18 RIPK2 inhibitors selected from BindingDB database. The pharmacophore model validation was performed by multiple linear regression (MLR). The statistical quality of the model was evaluated by the correlation coefficient (R), squared correlation coefficient (R), explanatory variance (adjusted R), standard error of estimate (SEE), and variance ratio (F). The best pharmacophore model has one aromatic group (LEU24 residue interaction) and two hydrogen bonding acceptor groups (MET98 and TYR97 residues interaction), having a score of 24.739 with 14 aligned inhibitors, which were used in virtual screening via ZincPharmer server and the ZINC database (selected in function of the RMSD value). We determined theoretical values of biological activity (logRA) by MLR, pharmacokinetic and toxicology properties, and made molecular docking studies comparing binding affinity (kcal/mol) results with the most active compound of the study (ponatinib) and WEHI-345. Nine compounds from the ZINC database show satisfactory results, yielding among those selected, the compound ZINC01540228, as the most promising RIPK2 inhibitor. After binding free energy calculations, the following molecular dynamics simulations showed that the receptor protein's backbone remained stable after the introduction of ligands.
Alzheimer's disease (AD) is a progressive condition, where dementia symptoms gradually worsen. Biochemically the disease is characterized by the presence of neuritic plaques, neurofibrillary tangles, in addition to cholinergic dysfunction in the central nervous system. The role of the cholinergic neurotransmission in AD is the basis of the widely accepted cholinergic hypothesis. Some of the most relevant therapies for the treatment of the disease are based on the acetylcholinesterase (AChE) inhibitor activity; however, these therapies are not effective to stop the disease progression, but only can temporarily slow down the worsening of dementia symptoms, and improve quality of life of patients and their caregivers. In recent years, plant alkaloids extracted from Amaryllidaceae family have received great attention due to the well-known anti cholinergic activity. In this context, the purpose of this study was to apply the docking molecular in sílico analysis aiming to examine the recombinant human AChE enzyme (rhAChE) inhibitory activity displayed by different alkaloids from Amaryllidaceae family. Overall, the present results support the idea that alkaloids reported in this research are capable of interacting with rhAChE-binding sites.
Aim: Our aim was to quantify the influence of climate and land use on major fires that occurred during the 2020 drought over the Brazilian Pantanal region.
Secondary forests provide essential ecosystem services, especially in helping to mitigate climate change with the storage of carbon in the aboveground biomass of tree species. In this context, the present research aimed to analyze the spatial distribution of secondary forests and estimate the aboveground biomass accumulation of land cover of different ages in the state of Pará. The spatial patterns of the secondary forests in Pará state were evaluated with hot spot analysis algorithms using data from the TerraClass project for the 2004–2014 time period. The results showed that the spatial distribution of the secondary forests did not occur randomly in space, but suggested local geopolitical influences. The younger secondary forests had the most deforested areas during the study period. Approximately 5% of Pará had its secondary forests deforested in 2014. In general, the balance of the secondary forests was positive. The aboveground biomass accumulation differed according to the secondary forest ages during the study period as evaluated in two pilot areas. It was observed that the secondary forests > 10 years old in pilot area A had an average of 23% of old-growth forest aboveground biomass in the same area, while in pilot area B, the secondary forests > 10 years old had an average of 32.7% of old-growth forest aboveground biomass.
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