Multiresolution molecular dynamics simulations reveal the interplay between conformational variability and functional interactions in membrane-bound cytochrome P450 2B4.

Cytochrome P450 2B4 (CYP 2B4) is one of the best-characterized CYPs and serves as a key model system for understanding the mechanisms of microsomal class II CYPs, which metabolize most known drugs. The highly flexible nature of CYP 2B4 is apparent from crystal structures that show the active site with either a wide open or a closed heme binding cavity. Here, we investigated the conformational ensemble of the full-length CYP 2B4 in a phospholipid bilayer, using multiresolution molecular dynamics (MD) simulations.

High pressure ferroelectric-like semi-metallic state in Eu-doped BaTiO3.

We have conducted a detailed high-pressure (HP) investigation on Eu-doped BaTiO3 using angle-resolved x-ray diffraction, Raman spectroscopy, and dielectric permittivity measurements. The x-ray diffraction data analysis shows a pressure-induced structural phase transition from the ambient tetragonal to the mixed cubic and tetragonal phases above 1.4 GPa.

Role of electron and hole doping in the NdNiVO nanostructure.

Neodymium nickelate, NdNiO, attracts attention due to the simultaneous occurrence of several phase transitions around the same temperature. The electronic properties of NdNiO are extremely complex as structural distortion, electron correlation, charge ordering, and orbital overlapping play significant roles in the transitions. We report the effects of electron and hole injection doping a single 3d metal, V, in the NdNiO nanostructure to understand the variations in the electronic properties without any structural distortion.

A community effort in SARS-CoV-2 drug discovery.

The COVID-19 pandemic continues to pose a substantial threat to human lives and is likely to do so for years to come. Despite the availability of vaccines, searching for efficient small-molecule drugs that are widely available, including in low- and middle-income countries, is an ongoing challenge. In this work, we report the results of an open science community effort, the "Billion molecules against COVID-19 challenge", to identify small-molecule inhibitors against SARS-CoV-2 or relevant human receptors.

Comparative analysis of drug-salt-polymer interactions by experiment and molecular simulation improves biopharmaceutical performance.

The propensity of poorly water-soluble drugs to aggregate at supersaturation impedes their bioavailability. Supersaturated amorphous drug-salt-polymer systems provide an emergent approach to this problem. However, the effects of polymers on drug-drug interactions in aqueous phase are largely unexplored and it is unclear how to choose an optimal salt-polymer combination for a particular drug.

Quantifying Functional-Group-like Structural Fragments in Molecules and Its Applications in Drug Design.

A functional group in a molecule is a structural fragment consisting of a few atoms or a single atom that imparts reactivity to a molecule. Hence, defining functional groups is crucial in chemistry to predict the properties and reactivities of molecules. However, there is no established method in the literature for defining functional groups based on reactivity parameters.

Air and water stable germacarbonyl compounds.

Germacarbonyl compounds are the germanium analogs of carbonyl compounds requiring an inert atmosphere for stability. Making these compounds survive the ambient conditions was not feasible given the lability of the Ge[double bond, length as m-dash]E bonds (E = O, S, Se, Te). However, the first examples of germacarbonyl compounds synthesized under ambient conditions by taking advantage of dipyrromethene ligand stabilization are detailed here; the isolated compounds are thiogermanone 3, selenogermanone 4, thiogermacarboxylic acid 6, selenogermacarboxylic acid 7, thiogermaester 9, selenogermaester 10, thiogermaamide 12, and selenogermaamide 13 with Ge[double bond, length as m-dash]E bonds (E = S, Se).

Hesperidin and hesperetin against heavy metal toxicity: Insight on the molecular mechanism of mitigation.

Toxic heavy metals (THMs) are non-essential hazardous environmental pollutants with intractable health challenges in humans and animals. Exposure to lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As), nickel (Ni), and chromium (Cr) are ubiquitous and unavoidable due to food contamination, mining, and industrial mobilization. They are triggers of tissue impairment and aberrant signaling pathways that cascade into several toxicities and pathologies.

Cloning, expression and characterization of PURase gene from Pseudomonas sp. AKS31.

Polyurethane (PUR) is a soil and aquatic contaminant throughout the world. Towards bioremediation, in a previous study, a soil bacterium, Pseudomonas sp. AKS31, capable of efficiently degrading PUR was isolated.

Omicron variant infection and the associated immunological scenario.

The million-dollar question that has been the talk of the day is how effective the COVID 19 vaccines are against the Omicron variant. Still, there is no clear-cut answer to this question but several studies have concluded that this Variant of Concern (VOC) successfully weakens the neutralizing capability of the antibodies acquired from the COVID 19 vaccines and prior infections, which indicates that Omicron can easily bypass an individual's humoral immune response. However, the most significant confusion revolves around cell-mediated immunity tackling the Omicron variant.

Mixed Contaminants: Occurrence, Interactions, Toxicity, Detection, and Remediation.

The ever-increasing rate of pollution has attracted considerable interest in research. Several anthropogenic activities have diminished soil, air, and water quality and have led to complex chemical pollutants. This review aims to provide a clear idea about the latest and most prevalent pollutants such as heavy metals, PAHs, pesticides, hydrocarbons, and pharmaceuticals-their occurrence in various complex mixtures and how several environmental factors influence their interaction.

Heavy metal and metalloid - induced reproductive toxicity.

Heavy metals and metalloid exposure are among the most common factors responsible for reproductive toxicity in human beings. Several studies have indicated that numerous metals and metalloids can display severe adverse properties on the human reproductive system. Metals like lead, silver, cadmium, uranium, vanadium, and mercury and metalloids like arsenic have been known to induce reproductive toxicity.

Anomalous structural behavior and antiferroelectricity in BiGdO: detailed temperature and high-pressure study.

A comprehensive temperature and high-pressure investigation on BiGdOis carried out by means of dielectric constant, piezoelectric current, polarization-electric field loop, Raman scattering and x-ray diffraction measurements. Temperature dependent dielectric constant and dielectric loss show two anomalies at about 290 K () and 720 K (). The latter anomaly is most likely due to antiferroelectric to paraelectric transition as hinted by piezoelectric current and polarization-electric field loop measurements at room temperature, while the former anomaly suggests reorientation of polarization.

A review on modern and smart technologies for efficient waste disposal and management.

In the current scenario, the word waste management holds much importance in every individual's life. Pollution and the generation of vast waste quantities with no proper waste management process have become one of humanity's biggest threats. This review article provides a complete review of the innovative technologies currently employed to handle and dispose of the waste successfully.

A Prelude to Biogermylene Chemistry*.

The biological applications of germylenes remain unrealised owing to their unstable nature. We report the isolation of air-, water-, and culture-medium-stable germylene DPMGeOH (3; DPM=dipyrromethene ligand) and its potential biological application. Compound 3 exhibits antiproliferative effects comparable to that of cisplatin in human cancer cells.

Isolation of a soil bacterium for remediation of polyurethane and low-density polyethylene: a promising tool towards sustainable cleanup of the environment.

Unlabelled: A soil bacterium, designated strain AKS31, was isolated on the plastic polyurethane (PUR) and based on the molecular and biochemical analysis was tentatively assigned to the genus . Preliminary studies suggested that strain AKS31 had the capability of biodegrading polyurethane (PUR) and low-density polyethylene (LDPE). This observation was confirmed by the analysis of the biodegradation products.

An electron transfer competent structural ensemble of membrane-bound cytochrome P450 1A1 and cytochrome P450 oxidoreductase.

Cytochrome P450 (CYP) heme monooxygenases require two electrons for their catalytic cycle. For mammalian microsomal CYPs, key enzymes for xenobiotic metabolism and steroidogenesis and important drug targets and biocatalysts, the electrons are transferred by NADPH-cytochrome P450 oxidoreductase (CPR). No structure of a mammalian CYP-CPR complex has been solved experimentally, hindering understanding of the determinants of electron transfer (ET), which is often rate-limiting for CYP reactions.

RASPD+: Fast Protein-Ligand Binding Free Energy Prediction Using Simplified Physicochemical Features.

The virtual screening of large numbers of compounds against target protein binding sites has become an integral component of drug discovery workflows. This screening is often done by computationally docking ligands into a protein binding site of interest, but this has the drawback of a large number of poses that must be evaluated to obtain accurate estimates of protein-ligand binding affinity. We here introduce a fast pre-filtering method for ligand prioritization that is based on a set of machine learning models and uses simple pose-invariant physicochemical descriptors of the ligands and the protein binding pocket.

Edible marine algae: a new source for anti-mycobacterial agents.

Tuberculosis is a dreaded disease, which causes innumerable death worldwide. The emergence of drug resistance strains makes the situation devastating. Therefore, for better management of public health, it is mandatory to search for new anti-mycobacterial agents.

The Effect of Force-Field Parameters on Cytochrome P450-Membrane Interactions: Structure and Dynamics.

The simulation of membrane proteins requires compatible protein and lipid force fields that reproduce the properties of both the protein and the lipid bilayer. Cytochrome P450 enzymes are bitopic membrane proteins with a transmembrane helical anchor and a large cytosolic globular domain that dips into the membrane. As such, they are representative and challenging examples of membrane proteins for simulations, displaying features of both peripheral and integral membrane proteins.

Mechanically interlocked architecture aids an ultra-stiff and ultra-hard elastically bendable cocrystal.

Molecular crystals are not known to be as stiff as metals, composites and ceramics. Here we report an exceptional mechanical stiffness and high hardness in a known elastically bendable organic cocrystal [caffeine (CAF), 4-chloro-3-nitrobenzoic acid (CNB) and methanol (1:1:1)] which is comparable to certain low-density metals. Spatially resolved atomic level studies reveal that the mechanically interlocked weak hydrogen bond networks which are separated by dispersive interactions give rise to these mechanical properties.

Donor-acceptor-stabilised germanium analogues of acid chloride, ester, and acyl pyrrole compounds: synthesis and reactivity.

Germaacid chloride, germaester, and -germaacyl pyrrole compounds were not known previously. Therefore, donor-acceptor-stabilised germaacid chloride (i-Bu)ATIGe(O)(Cl) → B(CF) (), germaester (i-Bu)ATIGe(O)(OSiPh) → B(CF) (), and -germaacyl pyrrole (i-Bu)ATIGe(O)(NCH) → B(CF) () compounds, with Cl-Ge[double bond, length as m-dash]O, PhSiO-Ge[double bond, length as m-dash]O, and CHN-Ge[double bond, length as m-dash]O moieties, respectively, are reported here. Germaacid chloride reacts with PhCCLi, KO-Bu, and RLi (R = Ph, Me) to afford donor-acceptor-stabilised germaynone (i-Bu)ATIGe(O)(CCPh) → B(CF) (), germaester (i-Bu)ATIGe(O)(O-Bu) → B(CF) (), and germanone (i-Bu)ATIGe(O)(R) → B(CF) (R = Ph , Me ) compounds, respectively.

Pressure induced anomalous magnetic behaviour in nanocrystalline YCrO at room temperature.

High pressure behaviour of nanocrystalline YCrO is investigated up to 10 GPa using electrical, magnetic, synchrotron x-ray diffraction and Raman spectroscopy measurements. High pressure dielectric constant measurements show a sharp peak at 4.5 GPa, though the sample is found to be in ferroelectric phase up to the highest pressure of our study from piezoelectric current measurements.

Pseudohalogenogermylenes versus Halogenogermylenes: Difference in their Complexation Behavior towards Group 6 Metal Carbonyls.

Pseudohalogenogermylenes [(iBu) ATI]GeY (Y=NCO 4, NCS 5) show different coordination behavior towards group 6 metal carbonyls in comparison to the corresponding halogenogermylenes [(iBu) ATI]GeX (X=F 1, Cl 2, Br 3) (ATI=aminotroponiminate). The reactions of compounds 4-5 and 1-3 with cis-[M(CO) (COD)] (M=Mo, W, COD=cyclooctadiene) gave trans-germylene metal complexes {[(iBu) ATI]GeY} M(CO) (Y=NCO, M=Mo 6, W 11; Y=NCS, M=Mo 7) and cis-germylene metal complexes {[(iBu) ATI]GeX} M(CO) (M=Mo, X=F 8, Cl 9, Br 10; M=W, X=Cl 12), respectively. Theoretical studies on compounds 7 and 9 reveal that donor-acceptor interactions from Mo to Ge atoms are better stabilized in the observed trans and cis geometries than in the hypothetical cis and trans structures, respectively.