Domain Mobility in the ORF2p Complex Revealed by Molecular Dynamics Simulations and Big Data Analysis.

ORF2p (open reading frame 2 protein) is a multifunctional multidomain enzyme that demonstrates both reverse transcriptase and endonuclease activities and is associated with the pathophysiology of cancer. The 3D structure of the entire seven-domain ORF2p complex was revealed with the recent achievements in structural studies. The different arrangements of the CTD (carboxy-terminal domain) and tower domains were identified as the "closed-ring" and "open-ring" conformations, which differed by the hairpin position of the tower domain, but the structural diversity of these complexes has the potential to be more extensive.

Systematic ab initio calculation of spectroscopic constants for A-reduced rotational effective Hamiltonians of asymmetric top molecules using normal ordering of cylindrical angular momentum operators.

This research paper presents a new fundamental approach for evaluating accurate ab initio quartic, sextic, and octic centrifugal distortion parameters of A-reduced rotational effective Hamiltonians of asymmetric top molecules. In this framework, the original Watson Hamiltonian, expanded up to sextic terms of kinetic and potential energies, is subjected to a series of vibrational and rotational operator unitary transformations, leading to reduced Watson effective Hamiltonians for the equilibrium configuration, ground state, and weakly perturbed vibrationally excited states. The proposed scheme is based on a numerical-analytic implementation of the sixth-order Van Vleck operator perturbation theory with the systematic normal ordering of vibrational rising and lowering operators (a†, a) and cylindrical angular momentum operators (Jz, J+, J-).

Quantification of cancer biomarkers in urine using volatilomic approach.

Urine analysis is an attractive approach for non-invasive cancer diagnostics. In this study, a procedure for the determination of volatile organic compounds (VOCs) in human urine (acetone, acetonitrile, dimethylsulfide, dimethyl disulfide, dimethyl trisulfide, hexane, benzene, toluene, 2-butanone, 2-pentanone, pentanal) has been described including sample preparation using preconcentration of analytes in sorbent tubes followed by gas chromatography with mass spectrometry (GC-MS). Fractional factorial design and constrained surfaces design were used to optimize preconcentration of VOCs in sorbent tubes.

Diagnosis of Lung Cancer Through Exhaled Breath: A Comprehensive Study.

Objectives: Exhaled breath analysis is an attractive lung cancer diagnostic tool. However, various factors that are not related to the disease status, comorbidities, and other diseases must be considered to obtain a reliable diagnostic model.

Methods: Exhaled breath samples from 646 individuals including 273 patients with lung cancer (LC), 90 patients with cancer of other localizations (OC), 150 patients with noncancer lung diseases (NLD), and 133 healthy controls (HC) were analyzed using gas chromatography-mass spectrometry (GC-MS).

A highly specific aptamer for the SARS-CoV-2 spike protein from the authentic strain.

DNA aptamers are oligonucleotides that specifically bind to target molecules, similar to how antibodies bind to antigens. We identified an aptamer named MEZ that is highly specific to the receptor-binding domain, RBD, of the SARS-CoV-2 spike protein from the Wuhan-Hu-1 strain. The SELEX procedure was utilized to enrich the initial 31-mer oligonucleotide library with the target aptamer.

Correction to "Non-invasive Exhaled Breath and Skin Analysis to Diagnose Lung Cancer: Study of Age Effect on Diagnostic Accuracy".

[This corrects the article DOI: 10.1021/acsomega.2c06132.

Selectivity of Exhaled Breath Biomarkers of Lung Cancer in Relation to Cancer of Other Localizations.

Lung cancer is a leading cause of death worldwide, mostly due to diagnostics in the advanced stage. Therefore, the development of a quick, simple, and non-invasive diagnostic tool to identify cancer is essential. However, the creation of a reliable diagnostic tool is possible only in case of selectivity to other diseases, particularly, cancer of other localizations.

Fluctuating Atlantic inflows modulate Arctic atlantification.

Enhanced warm, salty subarctic inflows drive high-latitude atlantification, which weakens oceanic stratification, amplifies heat fluxes, and reduces sea ice. In this work, we show that the atmospheric Arctic Dipole (AD) associated with anticyclonic winds over North America and cyclonic winds over Eurasia modulates inflows from the North Atlantic across the Nordic Seas. The alternating AD phases create a "switchgear mechanism.

Multiscale Simulations of the Covalent Inhibition of the SARS-CoV-2 Main Protease: Four Compounds and Three Reaction Mechanisms.

We report the results of computational modeling of the reactions of the SARS-CoV-2 main protease (M) with four potential covalent inhibitors. Two of them, carmofur and nirmatrelvir, have shown experimentally the ability to inhibit M. Two other compounds, X77A and X77C, were designed computationally in this work.

Non-Invasive Lung Cancer Diagnostics through Metabolites in Exhaled Breath: Influence of the Disease Variability and Comorbidities.

Non-invasive, simple, and fast tests for lung cancer diagnostics are one of the urgent needs for clinical practice. The work describes the results of exhaled breath analysis of 112 lung cancer patients and 120 healthy individuals using gas chromatography-mass spectrometry (GC-MS). Volatile organic compound (VOC) peak areas and their ratios were considered for data analysis.

Modeling Light-Induced Chromophore Hydration in the Reversibly Photoswitchable Fluorescent Protein Dreiklang.

We report the results of a computational study of the mechanism of the light-induced chemical reaction of chromophore hydration in the fluorescent protein Dreiklang, responsible for its switching from the fluorescent ON-state to the dark OFF-state. We explore the relief of the charge-transfer excited-state potential energy surface in the ON-state to locate minimum energy conical intersection points with the ground-state energy surface. Simulations of the further evolution of model systems allow us to characterize the ground-state reaction intermediate tentatively suggested in the femtosecond studies of the light-induced dynamics in Dreiklang and finally to arrive at the reaction product.

Non-invasive Exhaled Breath and Skin Analysis to Diagnose Lung Cancer: Study of Age Effect on Diagnostic Accuracy.

Development of simple, fast, and non-invasive tests for lung cancer diagnostics is essential for clinical practice. In this paper, exhaled breath and skin were studied as potential objects to diagnose lung cancer. The influence of age on the performance of diagnostic models was studied.

Quantum-based Modeling of Protein-ligand Interaction: The Complex of RutA with Uracil and Molecular Oxygen.

Modern quantum-based methods are employed to model interaction of the flavin-dependent enzyme RutA with the uracil and oxygen molecules. This complex presents the structure of reactants for the chain of chemical reactions of monooxygenation in the enzyme active site, which is important in drug metabolism. In this case, application of quantum-based approaches is an essential issue, unlike conventional modeling of protein-ligand interaction with force fields using molecular mechanics and classical molecular dynamics methods.

Development and Processing of New Composite Materials Based on High-Performance Semicrystalline Polyimide for Fused Filament Fabrication (FFF) and Their Biocompatibility.

Samples of composite materials based on high-performance semicrystalline polyimide R-BAPB (based on the dianhydride R: 1,3-bis-(3',4,-dicarboxyphenoxy)benzene and diamine BAPB: 4,4'-bis-(4″-aminophenoxy)diphenyl)) filled with carbon nanofibers and micron-sized discrete carbon fibers were obtained by FFF printing for the first time. The viscosity of melts of the composites based on R-BAPB, thermal, mechanical characteristics of the obtained composite samples, their internal structure, and biocompatibility were studied. Simultaneously with FFF printing, samples were obtained by injection molding.

How Reproducible Are QM/MM Simulations? Lessons from Computational Studies of the Covalent Inhibition of the SARS-CoV-2 Main Protease by Carmofur.

This work explores the level of transparency in reporting the details of computational protocols that is required for practical reproducibility of quantum mechanics/molecular mechanics (QM/MM) simulations. Using the reaction of an essential SARS-CoV-2 enzyme (the main protease) with a covalent inhibitor (carmofur) as a test case of chemical reactions in biomolecules, we carried out QM/MM calculations to determine the structures and energies of the reactants, the product, and the transition state/intermediate using analogous QM/MM models implemented in two software packages, NWChem and Q-Chem. Our main benchmarking goal was to reproduce the key energetics computed with the two packages.

Exhaled breath analysis using GC-MS and an electronic nose for lung cancer diagnostics.

Exhaled breath analysis is an interesting and promising approach for the diagnostics of various diseases. Being non-invasive, convenient and simple, this approach has tremendous potential utility for further translation into clinical practice. In this study, gas chromatography-mass spectrometry (GC-MS) and quartz microbalance sensor-based "electronic nose" were applied for analysis of the exhaled breath of 40 lung cancer patients and 40 healthy individuals.

Protonation States of Molecular Groups in the Chromophore-Binding Site Modulate Properties of the Reversibly Switchable Fluorescent Protein rsEGFP2.

The role of protonation states of the chromophore and its neighboring amino acid side chains of the reversibly switching fluorescent protein rsEGFP2 upon photoswitching is characterized by molecular modeling methods. Numerous conformations of the chromophore-binding site in computationally derived model systems are obtained using the quantum chemistry and QM/MM approaches. Excitation energies are computed using the extended multiconfigurational quasidegenerate perturbation theory (XMCQDPT2).

Study of confounding factors influence on lung cancer diagnostics effectiveness using gas chromatography-mass spectrometry analysis of exhaled breath.

The purpose of this study was to estimate volatile organic compounds (VOCs) ability to distinguish exhaled breath samples of lung cancer patients and healthy volunteers and to assess the effect of smoking status and gender on parameters. Exhaled breath samples of 40 lung cancer patients and 40 healthy individuals were analyzed using gas chromatography-mass spectrometry. Influence of other factors on the exhaled breath VOCs profile was investigated.

Stalling chromophore synthesis of the fluorescent protein Venus reveals the molecular basis of the final oxidation step.

Fluorescent proteins (FPs) have revolutionised the life sciences, but the mechanism of chromophore maturation is still not fully understood. Here we show that incorporation of a photo-responsive non-canonical amino acid within the chromophore stalls maturation of Venus, a yellow FP, at an intermediate stage; a crystal structure indicates the presence of O located above a dehydrated enolate form of the imidazolone ring, close to the strictly conserved Gly67 that occupies a twisted conformation. His148 adopts an "open" conformation so forming a channel that allows O access to the immature chromophore.

Modeling photophysical properties of the bacteriophytochrome-based fluorescent protein IFP1.4.

An enhanced interest in the phytochrome-based fluorescent proteins is explained by their ability to absorb and emit light in the far-red and infra-red regions particularly suitable for bioimaging. The fluorescent protein IFP1.4 was engineered from the chromophore-binding domain of a bacteriophytochrome in attempts to increase the fluorescence quantum yield.

Interplay between Locally Excited and Charge Transfer States Governs the Photoswitching Mechanism in the Fluorescent Protein Dreiklang.

We present the results of high-level electronic structure and dynamics simulations of the photoactive protein Dreiklang. With the goal of understanding the details of the Dreiklang photocycle, we carefully characterize the excited states of the ON- and OFF-forms of Dreiklang. The key finding of our study is the existence of a low-lying excited state of a charge-transfer character in the neutral ON form and that population of this state, which is nearly isoenergetic with the locally excited bright state, initiates a series of steps that ultimately lead to the formation of the hydrated dark chromophore (OFF state).

Increasing riverine heat influx triggers Arctic sea ice decline and oceanic and atmospheric warming.

Arctic river discharge increased over the last several decades, conveying heat and freshwater into the Arctic Ocean and likely affecting regional sea ice and the ocean heat budget. However, until now, there have been only limited assessments of riverine heat impacts. Here, we adopted a synthesis of a pan-Arctic sea ice-ocean model and a land surface model to quantify impacts of river heat on the Arctic sea ice and ocean heat budget.

Arctic tidal current atlas.

Tidal and wind-driven near-inertial currents play a vital role in the changing Arctic climate and the marine ecosystems. We compiled 429 available moored current observations taken over the last two decades throughout the Arctic to assemble a pan-Arctic atlas of tidal band currents. The atlas contains different tidal current products designed for the analysis of tidal parameters from monthly to inter-annual time scales.

Structure of the Brain -Acetylaspartate Biosynthetic Enzyme NAT8L Revealed by Computer Modeling.

We report the results of computational modeling of a three-dimensional all-atom structure of the membrane-associated protein encoded by the gene, aspartate -acetyltransferase, which is essential for brain synthesis of -acetyl-l-aspartate (NAA). The lack of experimentally derived three-dimensional structures of NAT8L poses one of the obstacles in studies of the mechanism of NAA formation and understanding the precise role of NAA in neurological disorders. We apply a computational protocol employing the contact map prediction, folding, homology modeling, and refinement to obtain a structure of NAT8L with the aspartate and acetyl coenzyme A cofactors in the protein molecule.

Investigation of different approaches for exhaled breath and tumor tissue analyses to identify lung cancer biomarkers.

Development of early noninvasive methods for lung cancer diagnosis is among the most promising technologies, especially using exhaled breath as an object of analysis. Simple sample collection combined with easy and quick sample preparation, as well as the long-term stability of the samples, make it an ideal choice for routine analysis. The conditions of exhaled breath analysis by preconcentrating volatile organic compounds (VOCs) in sorbent tubes, two-stage thermal desorption and gas-chromatographic determination with flame-ionization detection have been optimized.