The serine protease, DegP exhibits proteolytic and chaperone activities, essential for cellular protein quality control and normal cell development in eukaryotes. The P. falciparum DegP is essential for the parasite survival and required to combat the oscillating thermal stress conditions during the infection, protein quality checks and protein homeostasis in the extra-cytoplasmic compartments, thereby establishing it as a potential target for drug development against malaria. Previous studies have shown that diisopropyl fluorophosphate (DFP) and the peptide SPMFKGV inhibit E. coli DegP protease activity. To identify novel potential inhibitors specific to PfDegP allosteric and the catalytic binding sites, we performed a high throughput in silico screening using Malaria Box, Pathogen Box, Maybridge library, ChEMBL library and the library of FDA approved compounds. The screening helped identify five best binders that showed high affinity to PfDegP allosteric (T0873, T2823, T2801, {"type":"entrez-protein","attrs":{"text":"RJC02337","term_id":"1480409465","term_text":"RJC02337"}}RJC02337, CD00811) and the catalytic binding site (T0078L, T1524, T2328, BTB11534 and 552691). Further, molecular dynamics simulation analysis revealed {"type":"entrez-protein","attrs":{"text":"RJC02337","term_id":"1480409465","term_text":"RJC02337"}}RJC02337, BTB11534 as the best hits forming a stable complex. WaterMap and electrostatic complementarity were used to evaluate the novel bio-isosteric chemotypes of {"type":"entrez-protein","attrs":{"text":"RJC02337","term_id":"1480409465","term_text":"RJC02337"}}RJC02337, that led to the identification of 231 chemotypes that exhibited better binding affinity. Further analysis of the top 5 chemotypes, based on better binding affinity, revealed that the addition of electron donors like nitrogen and sulphur to the side chains of butanoate group are more favoured than the backbone of butanoate group. In a nutshell, the present study helps identify novel, potent and Plasmodium specific inhibitors, using high throughput in silico screening and bio-isosteric replacement, which may be experimentally validated. 相似文献
Summary Thermal degradation under N2atmosphere and thermoxidative degradation under air atmosphere of increasingly grafting efficiency values (i.e. GE%=0.0 to 35.5) for starch and starch grafted with N-tert-butylacrylamide thermosensitive copolymers (starch-g-BAM) by Ozawa and Kissinger methods using thermogravimetric analysis
(TG) and differential scanning calorimetry techniques (DSC) at 10, 30 and 50% mass losses respectively have been studied.
Influence of physical inter and intra molecular interactions on grafting and consequently on activation energy of degradation
(Ea,d) was investigated using Ozawa's method, whereas linear dependence of Ea,don GE% by scaling relations using Kissinger's method was determined. Furthermore, the thermoxidative degradation induces the possibility
of molecular rearrangement, cyclization and partial crosslinking that is deduced from the activation energy of degradation
(Ea,d) and residual mass of TG profile. Thermal stability of starch does not alter as a result of different grafting efficiency
percentages. 相似文献
This article reports the magnetohydrodynamic (MHD) three-dimensional flow of viscoelastic fluid over a stretching surface with heat transfer. Mathematical analysis is formulated using convective boundary conditions. Computations of dimensionless velocity and temperature fields are presented. The tabulated values show excellent agreement between present and previous limiting analysis. Graphical results show the impact of embedded parameters entering into the problem. 相似文献
The thermal decomposition of Eucalptus Camaldulensis and Cotton Stalks at different heating rates showed three exothermic peaks. The heating rate is the factor that affects their sharpness and position. The peaks are sharp at low heating rates. IR spectra of pyrolized residue at different temperature were also studied. 相似文献
The mineral extraction activities may disturb the natural radioactivity, therefore current study aims to generate baseline data of natural radionuclides and anthropogenic 137Cs before the start of industrial activities. Gamma spectrometry and gross alpha and beta counting systems were used for activity measurement in environmental samples. In soil, the mean activity of 232Th, 226Ra, 40K and 137Cs were determined as 79 (66–117), 47 (34–80), 823 (602–1159) and 1.3 (1.1–4.5) Bq kg?1, respectively. The average annual effective dose rate (128.7 µSv h?1) in the study area was twice higher than world’s average value. Indoor hazard index was greater than unity at two places; therefore, proper ventilation is proposed during construction.
Journal of Radioanalytical and Nuclear Chemistry - The kinetics of Co ions sorption on CoTreat® was investigated in the 5–40 mg/L concentration range at a bulk temperature of... 相似文献