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-).

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.

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.

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.

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.

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).

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).

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.

Computational Modeling Reveals the Mechanism of Fluorescent State Recovery in the Reversibly Photoswitchable Protein Dreiklang.

The unique properties of the photoswitchable protein Dreiklang are attributed to a reversible hydration/dehydration reaction at the imidazolinone ring of the chromophore. Recovery of the fluorescent state, which is associated with a chemical reaction of the chromophore's dehydration, is an important part of the photocycle of this protein. Here we characterize the fluorescent (ON) and nonfluorescent (OFF) states of Dreiklang and simulate the thermal recovery reaction OFF → ON using computational approaches.

Improving the Design of the Triple-Decker Motif in Red Fluorescent Proteins.

We characterize computationally a red fluorescent protein (RFP) with the chromophore (Chro) sandwiched between two aromatic tyrosine rings in a triple-decker motif. According to the original proposal [ J. Phys.

Greater role for Atlantic inflows on sea-ice loss in the Eurasian Basin of the Arctic Ocean.

Arctic sea-ice loss is a leading indicator of climate change and can be attributed, in large part, to atmospheric forcing. Here, we show that recent ice reductions, weakening of the halocline, and shoaling of the intermediate-depth Atlantic Water layer in the eastern Eurasian Basin have increased winter ventilation in the ocean interior, making this region structurally similar to that of the western Eurasian Basin. The associated enhanced release of oceanic heat has reduced winter sea-ice formation at a rate now comparable to losses from atmospheric thermodynamic forcing, thus explaining the recent reduction in sea-ice cover in the eastern Eurasian Basin.

Everolimus-eluting stents stabilize plaque inflammation in vivo: assessment by intravascular fluorescence molecular imaging.

Aims: Inflammation drives atherosclerosis complications and is a promising therapeutic target for plaque stabilization. At present, it is unknown whether local stenting approaches can stabilize plaque inflammation in vivo. Here, we investigate whether everolimus-eluting stents (EES) can locally suppress plaque inflammatory protease activity in vivo using intravascular near-infrared fluorescence (NIRF) molecular imaging.

A Light-Induced Reaction with Oxygen Leads to Chromophore Decomposition and Irreversible Photobleaching in GFP-Type Proteins.

Photobleaching and photostability of proteins of the green fluorescent protein (GFP) family are crucially important for practical applications of these widely used biomarkers. On the basis of simulations, we propose a mechanism for irreversible bleaching in GFP-type proteins under intense light illumination. The key feature of the mechanism is a photoinduced reaction of the chromophore with molecular oxygen (O2) inside the protein barrel leading to the chromophore's decomposition.

Trajectory of the Arctic as an integrated system.

Although much remains to be learned about the Arctic and its component processes, many of the most urgent scientific, engineering, and social questions can only be approached through a broader system perspective. Here, we address interactions between components of the Arctic system and assess feedbacks and the extent to which feedbacks (1) are now underway in the Arctic and (2) will shape the future trajectory of the Arctic system. We examine interdependent connections among atmospheric processes, oceanic processes, sea-ice dynamics, marine and terrestrial ecosystems, land surface stocks of carbon and water, glaciers and ice caps, and the Greenland ice sheet.

Recent oceanic changes in the Arctic in the context of long-term observations.

This synthesis study assesses recent changes of Arctic Ocean physical parameters using a unique collection of observations from the 2000s and places them in the context of long-term climate trends and variability. Our analysis demonstrates that the 2000s were an exceptional decade with extraordinary upper Arctic Ocean freshening and intermediate Atlantic water warming. We note that the Arctic Ocean is characterized by large amplitude multi-decadal variability in addition to a long-term trend, making the link of observed changes to climate drivers problematic.

First-principles characterization of the energy landscape and optical spectra of green fluorescent protein along the A→I→B proton transfer route.

Structures and optical spectra of the green fluorescent protein (GFP) forms along the proton transfer route A→I→B are characterized by first-principles calculations. We show that in the ground electronic state the structure representing the wild-type (wt) GFP with the neutral chromophore (A-form) is lowest in energy, whereas the systems with the anionic chromophore (B- and I-forms) are about 1 kcal/mol higher. In the S65T mutant, the structures with the anionic chromophore are significantly lower in energy than the systems with the neutral chromophore.

Unusual emitting states of the kindling fluorescent protein: appearance of the cationic chromophore in the GFP family.

The kindling fluorescent protein (KFP), the Ala143Gly variant of the natural chromoprotein asFP595, is a prospective biomarker in live cells. Following the results of QM/MM calculations, we predict that excitation of the protein under certain conditions, favoring formation of KFP fractions with the neutral chromophore, should result in fluorescence from the cationic form of the chromophore which is unusual for the members of the green fluorescent protein family. Occurrence of the neutral form is due to a water wire connecting the chromophore with the exterior of the protein.

Triple-Decker Motif for Red-Shifted Fluorescent Protein Mutants.

Among fluorescent proteins (FPs) used as genetically encoded fluorescent tags, the red-emitting FPs are of particular importance as suitable markers for deep tissue imaging. Using electronic structure calculations, we predict a new structural motif for achieving red-shifted absorption and emission in FPs from the GFP family. By introducing four point mutations, we arrive to the structure with the conventional anionic GFP chromophore sandwiched between two tyrosine residues.

Toward Molecular-Level Characterization of Photoinduced Decarboxylation of the Green Fluorescent Protein: Accessibility of the Charge-Transfer States.

Irradiation of the green fluorescent protein (GFP) by intense violet or UV light leads to decarboxylation of the Glu222 side chain in the vicinity of the chromophore (Chro). This phenomenon is utilized in optical highlighters, such as photoactivatable GFP (PA-GFP). Using state-of-the-art quantum chemical calculations, we investigate the feasibility of the mechanism proposed in the experimental studies [van Thor et al.