Molecular dynamics simulation and docking analysis of NF-κB protein binding with sulindac acid.

It is of interest to document the Molecular Dynamics Simulation and docking analysis of NF-κB target with sulindac sodium in combating COVID-19 for further consideration. Sulindac is a nonsteroidal anti-inflammatory drug (NSAID) of the arylalkanoic acid class that is marketed by Merck under the brand name Clinoril. We show the binding features of sulindac sodium with NF-κB that can be useful in drug repurposing in COVID-19 therapy.

Size-resolved effective density of submicron particles during summertime in the rural atmosphere of Beijing, China.

Particle density is an important physical property of atmospheric particles. The information on high time-resolution size-resolved particle density is essential for understanding the atmospheric physical and chemical aging processes of aerosols particles. In the present study, a centrifugal particle mass analyzer (CPMA) combined with a differential mobility analyzer (DMA) was deployed to determine the size-resolved effective density of 50 to 350nm particles at a rural site of Beijing during summer 2016. The measured particle effective densities decreased with increasing particle sizes and ranged from 1.43 to 1.55g/cm3, on average. The effective particle density distributions were dominated by a mode peaked at around 1.5g/cm3 for 50 to 350nm particles. Extra modes with peaks at 1.0, 0.8, and 0.6g/cm3 for 150, 240, and 350nm particles, which might be freshly emitted soot particles, were observed during intensive primary emissions episodes. The particle effective densities showed a diurnal variation pattern, with higher values during daytime. A case study showed that the effective density of Aitken mode particles during the new particle formation (NPF) event decreased considerably, indicating the significant contribution of organics to new particle growth.

Identification of EPAC (Exchange Protein Activated by cAMP) bioinformatically as a potential signalling biomarker in Cardiovascular Disease (CVD) and its molecular docking by a lead molecule.

The present work delineates the combinatorial approach of firstly, creation of a centralized data-set comprising signalling proteins identified on the basis of altered expression, such as over-expression or repression of a set of signalling protein(s) leading to the cause of the disease, which is based on published reports screened through Pubmed and secondly, in the in silico creation of novel lead (drug) molecules and docking of identified signalling biomarkers using such drugs to investigate possibility of their future application in the model systems eventually. EPAC (Exchange Protein Activated by cAMP) emerges as a signalling biomarker in cases studied presently. Brefeldin, the known inhibitor of EPAC, though the mechanism yet unexplored, has been the molecule used as the pharmacophore for creation of lead drug molecule. Various modifications have been incorporated into the pharmacophore to increase the hydrophobic interactions for increasing the binding efficiency of the generated lead molecule. Side-chain modifications of the pharmacophore and refinement of data through firedock upon docking of EPAC with the modified pharmacophore yielded best results on the bases of atomic contact energy, van der Waal and partial electrostatic interactions as well as additional estimations of the binding free energy. Modifications of CH3 at C15 with COOH and H at C2 with OH in brefeldin showed the best docking results on the basis of protein-drug interaction parameters. The present work provides a clue in rational design of EPAC inhibitors which could be developed as drug lead in combating CVD.

Mobility in the structure of E.coli recQ helicase upon substrate binding as seen from molecular dynamics simulations.

RecQ helicases feature multiple domains in their structure, of which the helicase domain, the RecQ-Ct domain and the HRDC domains are well conserved among the SF2 helicases. The helicase domain and the RecQ-Ct domain constitute the catalytic core of the enzyme. The domain interfaces are the DNA binding sites which display significant conformational changes in our molecular dynamics simulation studies. The preferred conformational states of the DNA bound and unbound forms of RecQ appear to be quite different from each other. DNA binding induces inter-domain flexibility leading to hinge mobility between the domains. The divergence in the dynamics of the two structures is caused by changes in the interactions at the domain interface, which seems to propagate along the whole protein structure. This could be essential in ssDNA binding after strand separation, as well as aiding translocation of the RecQ protein like an inch-worm.

Sampling artifacts of acidity and ionic species in PM2.5.

Although sampling artifacts of acidity, ammonium, nitrate, and chloride in airborne particulate pollutants can be reduced by the use of denuders to absorb interfering gases, artifacts due to interparticle interactions still remain. In this study, the contribution of individual artifact reactions to particle evaporation and the effects of aerosol composition on the extents of sampling artifacts in PM2.5 were investigated. Samples were collected using a Harvard honeycomb denuder/filter-pack system at an urban site and a rural site in Hong Kong. The results show that the formation of artifacts can be categorized into two regimes: ammonium rich (AR) samples with a molar ratio [NH4+]/ [SO4(2-)] greater than 1.5 and ammonium poor (AP) samples with a molar ratio [NH4+]/[SO4(2-)] less than or equal to 1.5. The urban samples were all AR samples, and they were characterized by high nitrate and low in situ free acid concentrations. In contrast, the rural samples were all AP samples and they were characterized by low nitrate and high in situ free acid concentrations. We have developed a methodology to estimate the contribution of each artifact reaction to the sampling loss of nitrate, chloride, ammonium, and acidity. In the AR samples, the evaporation of HNO3 and HCl and concomitant evaporation of NH3 were the principal reactions in determining the extent of the sampling loss of nitrate and chloride. In the AP samples, the evaporation of HNO3 and HCl alone was the principal reaction instead, especially at high sampling loss. The in situ free acid concentration, a function of aerosol composition and ambient conditions, is a more useful parameter than strong acidity in understanding the sampling loss of acidity, nitrate, and chloride from the collected particles.