Different Forms of Disorder in NMDA-Sensitive Glutamate Receptor Cytoplasmic Domains Are Associated with Differences in Condensate Formation.

The N-methyl-D-aspartate (NMDA)-sensitive glutamate receptor (NMDAR) helps assemble downstream signaling pathways through protein interactions within the postsynaptic density (PSD), which are mediated by its intracellular C-terminal domain (CTD). The most abundant NMDAR subunits in the brain are GluN2A and GluN2B, which are associated with a developmental switch in NMDAR composition. Previously, we used single molecule fluorescence resonance energy transfer (smFRET) to show that the GluN2B CTD contained an intrinsically disordered region with slow, hop-like conformational dynamics.

Fuzzy supertertiary interactions within PSD-95 enable ligand binding.

The scaffold protein PSD-95 links postsynaptic receptors to sites of presynaptic neurotransmitter release. Flexible linkers between folded domains in PSD-95 enable a dynamic supertertiary structure. Interdomain interactions within the PSG supramodule, formed by DZ3, H3, and uanylate Kinase domains, regulate PSD-95 activity.

Epidemiological challenges in pandemic coronavirus disease (COVID-19): Role of artificial intelligence.

World is now experiencing a major health calamity due to the coronavirus disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus clade 2. The foremost challenge facing the scientific community is to explore the growth and transmission capability of the virus. Use of artificial intelligence (AI), such as deep learning, in (i) rapid disease detection from x-ray or computed tomography (CT) or high-resolution CT (HRCT) images, (ii) accurate prediction of the epidemic patterns and their saturation throughout the globe, (iii) forecasting the disease and psychological impact on the population from social networking data, and (iv) prediction of drug-protein interactions for repurposing the drugs, has attracted much attention.

Structure and conformational dynamics of toxin A.

toxin A and B (TcdA and TcdB) are two major virulence factors responsible for diseases associated with infection (CDI). Here, we report the 3.18-Å resolution crystal structure of a TcdA fragment (residues L843-T2481), which advances our understanding of the complete structure of TcdA holotoxin.

Probing Interdomain Linkers and Protein Supertertiary Structure In Vitro and in Live Cells with Fluorescent Protein Resonance Energy Transfer.

Many proteins are composed of independently-folded domains connected by flexible linkers. The primary sequence and length of such linkers can set the effective concentration for the tethered domains, which impacts rates of association and enzyme activity. The length of such linkers can be sensitive to environmental conditions, which raises questions as to how studies in dilute buffer relate to the highly-crowded cellular environment.

Understanding biochemical processes in the presence of sub-diffusive behavior of biomolecules in solution and living cells.

In order to maintain cellular function, biomolecules like protein, DNA, and RNAs have to diffuse to the target spaces within the cell. Changes in the cytosolic microenvironment or in the nucleus during the fulfillment of these cellular processes affect their mobility, folding, and stability thereby impacting the transient or stable interactions with their adjacent neighbors in the organized and dynamic cellular interior. Using classical Brownian motion to elucidate the diffusion behavior of these biomolecules is hard considering their complex nature.

Networks of electrostatic and hydrophobic interactions modulate the complex folding free energy surface of a designed βα protein.

The successful de novo design of proteins can provide insights into the physical chemical basis of stability, the role of evolution in constraining amino acid sequences, and the production of customizable platforms for engineering applications. Previous guanidine hydrochloride (GdnHCl; an ionic denaturant) experiments of a designed, naturally occurring βα fold, Di-III_14, revealed a cooperative, two-state unfolding transition and a modest stability. Continuous-flow mixing experiments in our laboratory revealed a simple two-state reaction in the microsecond to millisecond time range and consistent with the thermodynamic results.

Attenuation of the early events of α-synuclein aggregation: a fluorescence correlation spectroscopy and laser scanning microscopy study in the presence of surface-coated Fe3O4 nanoparticles.

The aggregation of α-synuclein (A-syn) has been implicated in the pathogenesis of Parkinson's disease (PD). Although the early events of aggregation and not the matured amyloid fibrils are believed to be responsible for the toxicity, it has been difficult to probe the formation of early oligomers experimentally. We studied the effect of Fe3O4 nanoparticle (NP) in the early stage of aggregation of A-syn using fluorescence correlation spectroscopy (FCS) and laser scanning microscopy.

Early sodium dodecyl sulfate induced collapse of α-synuclein correlates with its amyloid formation.

The aggregation of α-synuclein (A-syn) has been implicated strongly in Parkinson's disease (PD). In vitro studies established A-syn to be a member of the intrinsically disordered protein (IDP) family. This protein undergoes structural interconversion between an extended and a compact state, and this equilibrium influences the mechanism of its aggregation.

Studies of protein folding and dynamics using single molecule fluorescence spectroscopy.

Single molecule fluorescence spectroscopy is emerging as an extremely powerful and sensitive tool to study complex biological problems. Single molecule fluorescence measurements can extract useful information that is hidden in the ensemble averaged biophysical or biochemical studies by virtue of their wide range of spatial and temporal resolution capabilities. With these advantages, single molecule fluorescence spectroscopy enables us to monitor the conformational states and their dynamics in the form of statistical distribution or time trajectory of physical observables.

Fluorescence correlation spectroscopy study on the effects of the shape and size of a protein on its diffusion inside a crowded environment.

Fluorescence correlation spectroscopy (FCS) has been commonly used to study the diffusional and conformational fluctuations of labeled molecules at single-molecule resolution. Here, we explored the applications of FCS inside a polyacrylamide gel to study the effects of molecular weight and molecular shape in a crowded environment. To understand the effect of molecular weight, we carried out FCS experiments with four model systems of different molecular weights in the presence of varying concentrations of acrylamide.

Ag-TiO2 nanoparticle codoped SiO2 films on ZrO2 barrier-coated glass substrates with antibacterial activity in ambient condition.

Anatase TiO2 and Ag nanoparticles (NPs) codoped SiO2 films were prepared by the sol-gel method. Proportionate amounts of 3-(glycidoxypropyl)trimethoxysilane (GLYMO), tetraethylorthosilicate (TEOS) and 3-(methacryloxypropyl)trimethoxysilane (MEMO) derived inorganic-organic silica sol, commercially available dispersed anatase TiO2 NPs, and AgNO3 were used to prepare the sols. The films were prepared on ZrO2 (cubic) precoated soda-lime glass substrates by a single-dipping technique and heat-treated at 450 °C in air and H2/Ar atmosphere to obtain hard, relatively porous, and transparent coatings of thickness>600 nm.