Solvent effects on structural and thermochemical properties of p53 tumor-suppressor gene: a molecular modeling approach in drug design

The p53 tumor-suppressor protein is a cellular phosphoprotein and a negative regulator of cell growth. Most p53 mutations occur in exons 5–8 within the DNA-binding domain. Therefore, p53 can potentially be targeted with novel drugs designed to bind to a mutation and restore its stability or wild-type conformation. For the current study, Hartree–Fock calculations were used to investigate the solvent-induced effects of five different solvent media (acetone, ethanol, methanol, dimethyl sulfoxide, and water) on the thermochemical parameters and relative energies, and on the multinuclear nuclear magnetic resonance shielding tensors of oxygen, nitrogen, and phosphorus nuclei, of GAT. To understand how the solvent affects the mutation region (the “hot spot”) of p53, the relative energies of GAT in selected solvent media were determined. Some biological evidence suggested the structural stabilities of hot spots of GAT have the optimum temperature and solvent type for mutation. All the authors’ findings are in accordance with common biological phenomena. Another important objective of this study was to compare the hydration Gibbs free energies of CUA and GAT in water using two different approaches where the solvent was treated as a continuum of the constant at different levels of Hartree–Fock theory. The Gibbs hydration energy values obtained in water with the polarized continuum model directly applied on the isolated CUA and GAT sequences were compared with those determined from the hydrated models with four, six, and eight water molecule clusters around the hot spots uracil and adenine. The clustered structures of water molecules around the hot spots of GAT (in DNA level) and CUA (in transcriptional level) were found to be energetically favored. The results of this study provide a reliable insight into the nature of mutation processes, which is of utmost importance for the study of biochemical structures, and provide a basis for drug design

Nanoparticles of Conjugated Methotrexate-Human Serum Albumin: Preparation and Cytotoxicity Evaluations

Methotrexate-human serum albumin conjugates were developed by a simple carbodiimide reaction. Methotrexate-human serum albumin conjugates were then crosslinked with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide HCl (EDC) to form nanoparticles. The size of nanoparticles determined by laser light scattering and TEM was between 90–150 nm. Nanoparticles were very stable at physiologic conditions (PBS pH 7.4, 37∘C) and after incubation with serum. The effect of amount of EDC used for crosslinking on the particle size and free amino groups of nanoparticles was examined. The amount of crosslinker showed no significant effect on the size of nanoparticles but free amino groups of nanoparticles were decreased by increasing the crosslinker. The physicochemical interactions between methotrexate and human serum albumin were investigated by differential scanning calorimetry (DSC). Nanoparticles were more cytotoxic on T47D cells compared to free methotrexate. Moreover, methotrexate-human serum albumin nanoparticles decreased the IC50 value of methotrexate on T47D cells in comparison with free methotrexate

Enhancing the Specific Power of a PEM Fuel Cell Powered UAV with a Novel Bean-Shaped Flow Field

One of the marketing challenges of unmanned aerial vehicles (UAVs) for various applications is enhancing flight durability. Due to the superior characteristics of proton exchange membrane fuel cells (PEMFCs), they have the potential to reach a longer flight time and higher payload. In this regard, a numerical assessment of a UAV air-cooled PEMFC is carried out using a three-dimensional (3-D), multiphase, and non-isothermal model on three flow fields, i.e., unblocked bean-shaped, blocked bean-shaped, and parallel. Then, the results of single-cell modeling are generalized to the PEMFC stack to provide the power of 2.5 kW for a UAV. The obtained results indicate that the strategy of rising air stoichiometry for cooling performs well in the unblocked bean-shaped design, and the maximum temperature along the channel length reaches 331.5 K at the air stoichiometric of 30. Further, it is found that the best performance of a 2.5 kW PEMFC stack is attained by the bean-shaped design without blockage, of which its volume and mass power density are 1.1 kW L−1 and 0.2 kW kg−1, respectively. It is 9.4% lighter and 6.9% more compact than the parallel flow field. Therefore, the unblocked bean-shaped design can be a good option for aerial applications

Effects of assembly pressure on PEM fuel cell performance by taking into accounts electrical and thermal contact resistances

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