Conformational dynamics of a nicotinic receptor neurotransmitter site.

Agonists enhance receptor activity by providing net-favorable binding energy to active over resting conformations, with efficiency (η) linking binding energy to gating. Previously, we showed that in nicotinic receptors, η-values are grouped into five structural pairs, correlating efficacy and affinity within each class, uniting binding with allosteric activation (Indurthi and Auerbach, 2023). Here, we use molecular dynamics (MD) simulations to investigate the low-to-high affinity transition (L→H) at the Torpedo α-δ nicotinic acetylcholine receptor neurotransmitter site.

strategies to recognize pharmacological constraints contrary to COX-2 and 5-LOX.

COX-2 and 5-LOX are major enzymes implicated in inflammatory processes and have a crucial role in the pathogenesis of inflammatory disorders and malignancies. Designing antagonists that may concurrently interact with several receptors is a viable technique; thus, blocking these two targets with a single chemical compound might provide an efficient therapeutic approach. In-silico approaches have been employed to find polypharmacological inhibitors, especially for drug repurposing and multitarget drug design.

Structural insights into trypanosomatid Mnk kinase orthologues (kMnks) suggest altered mechanism in the kinase domain.

Mitogen-activated protein kinase (MAPK) interacting protein kinases (Mnk1 and Mnk2) mediated phosphorylation of the eukaryotic initiation factor eIF4E is an important translation initiation control, in Mnk-mediated oncogenic activity and other disease conditions. Thus, Mnk kinases are an important target for therapy. Trypanosomatids are a class of kinetoplastids, some of which are protozoan parasites and cause diseases in humans.

Compressive Properties of Additively Manufactured Metal-Reinforced PLA and ABS Composites.

The development of multi-material filaments has enabled fused filament fabrication-based additive manufacturing to address demand for high-performance lightweight multifunctional components. In this study, polylactic acid (PLA) and acrylonitrile butadiene styrene based filaments with metallic reinforcements of magnetic iron (MI), stainless steel (SS), bronze (Br), copper (Cu), Bismuth (Bi), and Tungsten (W) were investigated to elucidate their complex processing-structure-property relationships. The microstructure of 3D-printed materials were characterized by microscopy and analyzed to determine the metal cross-sectional area percentage and the relationship between metal reinforcement, the polymer matrix, and porosity.

Additively Manufactured Carbon-Reinforced ABS Honeycomb Composite Structures and Property Prediction by Machine Learning.

The expansive utility of polymeric 3D-printing technologies and demand for high- performance lightweight structures has prompted the emergence of various carbon-reinforced polymer composite filaments. However, detailed characterization of the processing-microstructure-property relationships of these materials is still required to realize their full potential. In this study, acrylonitrile butadiene styrene (ABS) and two carbon-reinforced ABS variants, with either carbon nanotubes (CNT) or 5 wt.

Mango Leaves ()-Derived Highly Florescent Green Graphene Quantum Dot Nanoprobes for Enhanced On-Off Dual Detection of Cholesterol and Fe Ions Based on Molecular Logic Operation.

In the present study, we have engineered a molecular logic gate system employing both Fe ions and cholesterol as bioanalytes for innovative detection strategies. We utilized a green-synthesis method employing the mango leaves extract to create fluorescent graphene quantum dots termed "mGQDs". Through techniques like HR-TEM, i.

Interfacial Tension-Temperature-Pressure-Salinity Relationship for the Hydrogen-Brine System under Reservoir Conditions: Integration of Molecular Dynamics and Machine Learning.

Hydrogen (H) underground storage has attracted considerable attention as a potentially efficient strategy for the large-scale storage of H. Nevertheless, successful execution and long-term storage and withdrawal of H necessitate a thorough understanding of the physical and chemical properties of H in contact with the resident fluids. As capillary forces control H migration and trapping in a subsurface environment, quantifying the interfacial tension (IFT) between H and the resident fluids in the subsurface is important.

Intradermal Immunization of Soluble Influenza HA Derived from a Lethal Virus Induces High Magnitude and Breadth of Antibody Responses and Provides Complete Protection In Vivo.

Immunogens mimicking the native-like structure of surface-exposed viral antigens are considered promising vaccine candidates. Influenza viruses are important zoonotic respiratory viruses with high pandemic potential. Recombinant soluble hemagglutinin (HA) glycoprotein-based protein subunit vaccines against Influenza have been shown to induce protective efficacy when administered intramuscularly.

SARS-CoV-2 envelope protein attain K mediated dynamical interaction network to adopt 'histone mimic' at BRD4 interface.

Interface mimicry, achieved by recognition of host-pathogen interactions, is the basis by which pathogen proteins can hijack the host machinery. The envelope (E) protein of SARS-CoV-2 is reported to mimic the histones at the BRD4 surface via establishing the structural mimicry; however, the underlying mechanism of E protein mimicking the histones is still elusive. To explore the mimics at dynamic and structural residual network level an extensive docking, and MD simulations were carried out in a comparative manner between complexes of H3-, H4-, E-, and apo-BRD4.

Multi-Material Additive Manufacturing of High Temperature Polyetherimide (PEI)-Based Polymer Systems for Lightweight Aerospace Applications.

Rapid innovations in 3-D printing technology have created a demand for multifunctional composites. Advanced polymers like amorphous thermoplastic polyetherimide (PEI) can create robust, lightweight, and efficient structures while providing high-temperature stability. This work manufactured ULTEM, a PEI-based polymer, and carbon-fiber-infused ULTEM multi-material composites with varying layering patterns (e.

Characterizing (un)binding mechanism of USP7 inhibitors to unravel the cause of enhanced binding potencies at allosteric checkpoint.

The ability to predict the intricate mechanistic behavior of ligands and associated structural determinants during protein-ligand (un)binding is of great practical importance in drug discovery. Ubiquitin specific protease-7 (USP7) is a newly emerging attractive cancer therapeutic target with bound allosteric inhibitors. However, none of the inhibitors have reached clinical trials, allowing opportunities to examine every aspect of allosteric modulation.

A common Matrix metalloproteinase 8 promoter haplotype enhances the risk for hypertension via diminished interactions with nuclear factor kappa B.

Objectives: Matrix metalloproteinase 8 (MMP8) has a prominent role in collagen turnover in blood vessels and vascular remodeling. The contribution of regulatory single nucleotide polymorphisms in MMP8 to cardiovascular diseases is unclear. We aimed to delineate the influence of MMP8 promoter variations on hypertension.

Effect of Reinforcements and 3-D Printing Parameters on the Microstructure and Mechanical Properties of Acrylonitrile Butadiene Styrene (ABS) Polymer Composites.

Fused filament fabrication (FFF) systems utilize a wide variety of commercially available filaments, including Acrylonitrile Butadiene Styrene (ABS), as well as their variants. However, the effect of filament composition, reinforcements (chopped fibers and nanotubes), and 3-D printing variables on the microstructure and thermomechanical behavior is not well understood, and systematic studies are needed. In this work, different types of ABS materials with and without carbon fiber and carbon nanotube reinforcements were printed with multiple print layer heights.

Design and synthesis of amino acid derivatives of substituted benzimidazoles and pyrazoles as Sirt1 inhibitors.

Owing to its presence in several biological processes, Sirt1 acts as a potential therapeutic target for many diseases. Here, we report the structure-based designing and synthesis of two distinct series of novel Sirt1 inhibitors, benzimidazole mono-peptides and amino-acid derived 5-pyrazolyl methylidene rhodanine carboxylic acid. The compounds were evaluated for enzyme-based and cell-based Sirt1 inhibition assay, and cytotoxic-activity in both liver and breast cancer cells.

Structure-based pharmacophore mapping and virtual screening of natural products to identify polypharmacological inhibitor against c-MET/EGFR/VEGFR-2.

Three receptor tyrosine kinases (RTKs), c-MET, EGFR, and VEGFR-2 have been identified as potential oncogenic targets involved in tumor development, metastasis, and invasion. Designing inhibitors that can simultaneously interact with multiple targets is a promising approach, therefore, inhibiting these three RTKs with a single chemical component might give an effective chemotherapeutic strategy for addressing the disease while limiting adverse effects. The methods have been developed to identify the polypharmacological inhibitors particularly for drug repurposing and multitarget drug design.

Additive Manufacturing and Characterization of Metal Particulate Reinforced Polylactic Acid (PLA) Polymer Composites.

Affordable commercial desktop 3-D printers and filaments have introduced additive manufacturing to all disciplines of science and engineering. With rapid innovations in 3-D printing technology and new filament materials, material vendors are offering specialty multifunctional metal-reinforced polymers with unique properties. Studies are necessary to understand the effects of filament composition, metal reinforcements, and print parameters on microstructure and mechanical behavior.

Preoperative COVID-19 Testing for Elective Ophthalmological Procedure in a Tertiary Health Care Centre: Our Experience During the Pandemic.

Background: To study the prevalence of coronavirus infection among asymptomatic patients requiring eye surgery and the role of screening in prevention of spread of infection among the healthcare workers.

Design: The prospective observational study was conducted in the Ophthalmology department of a tertiary care center in Delhi from September 2020 to December 2020.

Setting: Patients requiring elective ophthalmological procedures in a tertiary care hospital were screened for coronavirus using the RT-PCR method.

Is Interferon α-2b 1 MillionIU/mL Truly Better Than Tacrolimus 0.03% for Steroid-Resistant VKC ?: Our 2-Year Experience at a Tertiary Health-Care Centre.

Purpose: To compare the efficacy of eye-drop interferon (IFN) α-2b 1 millionIU/mL with eye-ointment tacrolimus 0.03% in refractory vernal keratoconjunctivitis (VKC).

Materials And Methods: Fifty patients with VKC refractory to conventional treatment with topical corticosteroids and antihistamines after 4 weeks of regular use were selected retrospectively.

Sentiment analysis on the impact of coronavirus in social life using the BERT model.

Nowadays, the whole world is confronting an infectious disease called the coronavirus. No country remained untouched during this pandemic situation. Due to no exact treatment available, the disease has become a matter of seriousness for both the government and the public.

Essential functional molecules associated with SARS-CoV-2 infection: Potential therapeutic targets for COVID-19.

The whole world is still suffering substantially from the coronavirus disease 2019 (COVID-19) outbreak. Several protein-based molecules that are associated with the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which are essential for its functionality, survival, and pathogenesis have been identified and are considered as potential therapeutic targets. These protein-based molecules are either structural/non-structural components of SARS-CoV-2 or host factors, which play a crucial role in this infection.

Identification of potential molecules against COVID-19 main protease through structure-guided virtual screening approach.

The pandemic caused by novel coronavirus disease 2019 (COVID-19) infecting millions of populations worldwide and counting, has demanded quick and potential therapeutic strategies. Current approved drugs or molecules under clinical trials can be a good pool for repurposing through techniques to quickly identify promising drug candidates. The structural information of recently released crystal structures of main protease (M) in APO and complex with inhibitors, N3, and 13b molecules was utilized to explore the binding site architecture through Molecular dynamics (MD) simulations.

A Common Tag Nucleotide Variant in Promoter Increases Risk for Hypertension via Enhanced Interactions With CREB (Cyclic AMP Response Element-Binding Protein) Transcription Factor.

MMP (matrix metalloproteinase)-7-a potent extracellular matrix degrading enzyme-is emerging as a new regulator of cardiovascular diseases. However, potential contributions of genetic variations to hypertension remain unknown. In this study, we probed for the association of a tag single-nucleotide polymorphism in the promoter (-181A/G; rs11568818) with hypertension in an urban South Indian population (n=1501).

Molecular dynamics simulation reveals the possible druggable of USP7.

The plasticity in Ubiquitin Specific Proteases (USP7) inducing conformational changes at important areas has highlighted an intricate mechanism, by which USP7 is regulated. Given the importance of USP7 in oncogenic pathways and immune-oncology, identification of USP7 inhibitors has attracted considerable interest. Despite substantial efforts, the discovery of deubiquitinases (DUBs) inhibitors, knowledge of their binding site and understanding the possible mechanism of action has proven particularly challenging.