Is Protein Folding a Thermodynamically Unfavorable, Active, Energy-Dependent Process?

The prevailing current view of protein folding is the thermodynamic hypothesis, under which the native folded conformation of a protein corresponds to the global minimum of Gibbs free energy G. We question this concept and show that the empirical evidence behind the thermodynamic hypothesis of folding is far from strong. Furthermore, physical theory-based approaches to the prediction of protein folds and their folding pathways so far have invariably failed except for some very small proteins, despite decades of intensive theory development and the enormous increase of computer power. The recent spectacular successes in protein structure prediction owe to evolutionary modeling of amino acid sequence substitutions enhanced by deep learning methods, but even these breakthroughs provide no information on the protein folding mechanisms and pathways. We discuss an alternative view of protein folding, under which the native state of most proteins does not occupy the global free energy minimum, but rather, a local minimum on a fluctuating free energy landscape. We further argue that ΔG of folding is likely to be positive for the majority of proteins, which therefore fold into their native conformations only through interactions with the energy-dependent molecular machinery of living cells, in particular, the translation system and chaperones. Accordingly, protein folding should be modeled as it occurs in vivo, that is, as a non-equilibrium, active, energy-dependent process.

A Significant Detection of X-ray Polarization in Sco X-1 with PolarLight and Constraints on the Corona Geometry

We report the detection of X-ray polarization in the neutron-star low-mass X-ray binary Scorpius (Sco) X-1 with PolarLight. The result is energy-dependent, with a nondetection in 3–4 keV but a 4σ detection in 4–8 keV; it is also flux-dependent in the 4–8 keV band, with a nondetection when the source displays low fluxes but a 5σ detection during high fluxes, in which case we obtain a polarization fraction of 0.043 ± 0.008 and a polarization angle of 52.°6 ± 5.°4. This confirms a previous marginal detection with OSO-8 in the 1970s and marks Sco X-1 as the second astrophysical source with a significant polarization measurement in the keV band. The measured polarization angle is in line with the jet orientation of the source on the sky plane (54°), which is supposedly the symmetry axis of the system. Combining previous spectral analysis, our measurements suggest that an optically thin corona is located in the transition layer under the highest accretion rates, and disfavor the extended accretion disk corona model.

Confinement in bilayer graphene via intra- and inter-layer interactions

We consider confinement of Dirac fermions in AB-stacked bilayer graphene by inhomogeneous on-site interactions, (pseudo-)magnetic field or inter-layer interaction. Working within the framework of four-band approximation, we focus on the systems where the stationary equation is reducible into two stationary equations with 2x2 Dirac-type Hamiltonians and auxiliary interactions. We show that the localized states are given in terms of solutions of an effective Schrodinger equation with energy-dependent potential. We consider several scenarios where bilayer graphene is subject to inhomogneous (pseudo-)magnetic field, on-site interactions or inter-layer coupling. In explicit examples, we provide analytical solutions for the states localized by local fluctuations or periodicity defects of the interactions.

A Thermodynamic Model for Interpreting Tryptophan Excitation-Energy-Dependent Fluorescence Spectra Provides Insight Into Protein Conformational Sampling and Stability

It is now over 30 years since Demchenko and Ladokhin first posited the potential of the tryptophan red edge excitation shift (REES) effect to capture information on protein molecular dynamics. While there have been many key efforts in the intervening years, a biophysical thermodynamic model to quantify the relationship between the REES effect and protein flexibility has been lacking. Without such a model the full potential of the REES effect cannot be realized. Here, we present a thermodynamic model of the tryptophan REES effect that captures information on protein conformational flexibility, even with proteins containing multiple tryptophan residues. Our study incorporates exemplars at every scale, from tryptophan in solution, single tryptophan peptides, to multitryptophan proteins, with examples including a structurally disordered peptide, de novo designed enzyme, human regulatory protein, therapeutic monoclonal antibodies in active commercial development, and a mesophilic and hyperthermophilic enzyme. Combined, our model and data suggest a route forward for the experimental measurement of the protein REES effect and point to the potential for integrating biomolecular simulation with experimental data to yield novel insights.

B- and N-doped carbon dots by one-step microwave hydrothermal synthesis: tracking yeast status and imaging mechanism

Background Carbon dots (CDs) are widely used in cell imaging due to their excellent optical properties, biocompatibility and low toxicity. At present, most of the research on CDs focuses on biomedical application, while there are few studies on the application of microbial imaging. Results In this study, B- and N-doped carbon dots (BN-CDs) were prepared from citric acid, ethylenediamine, and boric acid by microwave hydrothermal method. Based on BN-CDs labeling yeast, the dead or living of yeast cell could be quickly identified, and their growth status could also be clearly observed. In order to further observe the morphology of yeast cell under different lethal methods, six methods were used to kill the cells and then used BN-CDs to label the cells for imaging. More remarkably, imaging of yeast cell with ultrasound and antibiotics was significantly different from other imaging due to the overflow of cell contents. In addition, the endocytosis mechanism of BN-CDs was investigated. The cellular uptake of BN-CDs is dose, time and partially energy-dependent along with the involvement of passive diffusion. The main mechanism of endocytosis is caveolae-mediated. Conclusion BN-CDs can be used for long-term stable imaging of yeast, and the study provides basic research for applying CDs to microbiol imaging. Graphical Abstract

Energy-dependent Boundaries of Earth's Radiation Belt Electron Slot Region

The variations in radiation belt boundaries reflect competition between acceleration and loss physical processes of energetic electrons, which is an important issue for radiation belts of planets with an internal magnetic field (e.g., Earth, Jupiter, and Saturn). Based on high-quality measurements from Van Allen Probes spanning the years 2014–2018, we develop an empirical model of the energy-dependent boundaries of Earth's electron radiation belt slot region, showing that the lower boundary follows a logarithmic function of the electron energy while the upper boundary is controlled by two competing energy-dependent processes, namely compression and recovery. The compression process relates linearly to a 15 hr averaged Kp index, while the recovery process is found to be approximately proportional to time. Detailed data-model comparisons demonstrate that our model, using only the Kp index and time epoch as inputs, reconstructs the slot region boundaries in real time for 200 keV to 2 MeV electrons under varying geomagnetic conditions. Such a data-driven empirical model is prerequisite to understanding the dynamic changes of the slot region in response to both solar and geomagnetic activities. The model can be readily incorporated into future global simulations of radiation belt electron dynamics in Earth's inner magnetosphere and provide new insights into the study of Saturn's and Jupiter's radiation belt variability.

Molecular synthesis in ices triggered by dissociative electron attachment to carbon monoxide

Chemical reactions in mixed molecular ices as relevant in the context of astrochemistry can be initiated by electron-molecule interactions. Dissociative electron attachment (DEA) as initiating step is identified from the enhancement of product yields upon irradiation at particular electron energies. Herein, we show that DEA to CO leads to the formation of HCN in mixed CO/$$\hbox {NH}_{{3}}$$ NH 3 ice at electron energies around 11 eV and 16 eV. We propose that this reaction proceeds via insertion of the neutral C fragment into a N–H bond. In the case of CO/$$\hbox {H}_{{2}}$$ H 2 O and CO/$$\hbox {CH}_{{3}}$$ CH 3 OH ices, a resonant enhancement of the yields of HCOOH and $$\hbox {CH}_{{3}}$$ CH 3 OCHO, respectively, is observed around 10 eV. In both ices, both molecular constituents exhibit DEA processes in this energy range so that the energy-dependent product yield alone does not uniquely identify the relevant DEA channel. However, we demonstrate by comparing with earlier results on mixed ices where CO is replaced by $$\hbox {C}_{{2}}\hbox {H}_{{4}}$$ C 2 H 4 that DEA to CO is again responsible for the enhanced product formation. In this case, $$\hbox {O}^{\cdot -}$$ O · - activates $$\hbox {H}_{{2}}$$ H 2 O or $$\hbox {CH}_{{3}}$$ CH 3 OH which leads to the formation of larger products. We thus show that DEA to CO plays an important role in electron-induced syntheses in molecular ices. Graphical abstract

Phonon-assisted electronic states modulation of few-layer PdSe2 at terahertz frequencies

Information technology demands high-speed optoelectronic devices, but going beyond the one terahertz (THz) barrier is challenging due to the difficulties associated with generating, detecting, and processing high-frequency signals. Here, we show that femtosecond-laser-driven phonons can be utilized to coherently manipulate the excitonic properties of semiconductors at THz frequencies. The precise control of the pump and subsequent time-delayed broadband probe pulses enables the simultaneous generation and detection processes of both periodic lattice vibrations and their couplings with electronic states. Combining ultralow frequency Raman spectroscopy with first-principles calculations, we identify the unique phonon mode-selective and probe-energy dependent features of electron–phonon interactions in layered PdSe2. Two distinctive types of coherent phonon excitations could couple preferentially to different types of electronic excitations: the intralayer (4.3 THz) mode to carriers and the interlayer (0.35 THz) mode to excitons. This work provides new insights to understand the excited-state phonon interactions of 2D materials and to achieve future applications of optoelectronic devices operating at THz frequencies.