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Synchronous RNA conformational changes trigger ordered phase transitions in crystals

Time-resolved studies of biomacromolecular crystals have been limited to systems involving only minute conformational changes within the same lattice. Ligand-induced changes greater than several angstroms, however, are likely to result in solid-solid phase transitions, which require a detailed understanding of the mechanistic interplay between conformational and lattice transitions. Here we report the synchronous behavior of the adenine riboswitch aptamer RNA in crystal during ligand-triggered isothermal phase transitions. Direct visualization using polarized video microscopy and atomic force microscopy shows that the RNA molecules undergo cooperative rearrangements that maintain lattice order, whose cell parameters change distinctly as a function of time. The bulk lattice order throughout the transition is further supported by time-resolved diffraction data from crystals using an X-ray free electron laser. The synchronous molecular rearrangements in crystal provide the physical basis for studying large conformational changes using time-resolved crystallography and micro/nanocrystals.

Saminathan Ramakrishnan, Jason R. Stagno, Chelsie E. Conrad, Jienyu Ding, Ping Yu, Yuba R. Bhandari, Yun-Tzai Lee, Gary Pauly, Oleksandr Yefanov, Max O. Wiedorn, Juraj Knoska, Dominik Oberthür, Thomas A. White, Anton Barty, Valerio Mariani, Chufeng Li, Wolfgang Brehm, William F. Heinz, Valentin Magidson, Stephen Lockett, Mark S. Hunter, Sébastien Boutet, Nadia A. Zatsepin, Xiaobing Zuo, Thomas D. Grant, Suraj Pandey, Marius Schmidt, John C. H. Spence, Henry N. Chapman & Yun-Xing Wan

Nat Commun 12, 1762 (2021). https://doi.org/10.1038/s41467-021-21838-5
  • in science
  • 1 min read

Active learning of potential-energy surfaces of weakly-bound complexes with regression-tree ensembles

Several pool-based active learning algorithms were employed to model potential energy surfaces (PESs) with a minimum number of electronic structure calculations. Among these algorithms, the class of uncertainty-based algorithms are popular. Their key principle is to query molecular structures corresponding to high uncertainties in their predictions. We empirically show that this strategy is not optimal for nonuniform data distributions as it collects many structures from sparsely sampled regions, which are less important to applications of the PES. We exploit a simple stochastic algorithm to correct for this behavior and implement it using regression trees, which have relatively small computational costs. We show that this algorithm requires around half the data to converge to the same accuracy than the uncertainty-based algorithm query-by-committee. Simulations on a 6D PES of pyrrole(H2O) show that <15000 configurations are enough to build a PES with a generalization error of 16 cm−1, whereas the final model with around 50000 configurations has a generalization error of 11 cm−1.

https://arxiv.org/abs/2104.00708

Yahya Saleh, Vishnu Sanjay, Armin Iske, Andrey Yachmenev, Jochen Küpper
  • in science
  • 1 min read

Scalable spectral solver in Galilean coordinates for eliminating the numerical Cherenkov instability in particle-in-cell simulations of streaming plasmas

Discretizing Maxwell's equations in Galilean (comoving) coordinates allows the derivation of a pseudospectral solver that eliminates the numerical Cherenkov instability for electromagnetic particle-in-cell simulations of relativistic plasmas flowing at a uniform velocity. Here we generalize this solver by incorporating spatial derivatives of arbitrary order, thereby enabling efficient parallelization by domain decomposition. This allows scaling of the algorithm to many distributed compute units. We derive the numerical dispersion relation of the algorithm and present a comprehensive theoretical stability analysis. The method is applied to simulations of plasma acceleration in a Lorentz-boosted frame of reference.

Kirchen, Manuel and Lehe, Remi and Jalas, Soeren and Shapoval, Olga and Vay, Jean-Luc and Maier, Andreas R
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Optimization and stability of a high-gain harmonic generation seeded oscillator amplifier

The free-electron laser (FEL) community is interested in taking full advantage of the high-repetition-rates of FELs run by superconducting machines while maintaining the spectral properties achieved with external seeding techniques. Since the feasibility of seed lasers operating at a repetition-rate of MHz and with sufficient energy in a useful wavelength range, such as the ultraviolet (UV) range is challenging, a seeded oscillator-amplifier scheme is proposed instead for generation of fully coherent and high-repetition-rate radiation. The process is triggered by an external seed laser while an optical feedback system feeds the radiation back to the entrance of the modulator where it overlaps with the next electron bunch. Downstream from the feedback system, the electron bunches are then used for harmonic generation. We discuss the optimization of dedicated simulations and we investigate the stability of this scheme with numerical simulations. As a result, we address the control of the reflectivity of the resonator as a key parameter to achieve a stable HGHG seeded radiation. Finally, we show the impact of the power fluctuations in the oscillator on the bunching amplitude with analytical and simulated results. The output FEL radiation wavelengths considered are 4.167 nm and 60 nm.

https://doi.org/10.1103/PhysRevAccelBeams.24.034801

Georgia Paraskaki, Vanessa Grattoni, Tino Lang, Johann Zemella, Bart Faatz, and Wolfgang Hillert
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  • 2 min read

Three-dimensional imaging of xylem at cell wall level through near field nano holotomography

Detailed imaging of the three-dimensionally complex architecture of xylary plants is important for studying biological and mechanical functions of woody plants. Apart from common two-dimensional microscopy, X-ray micro-computed tomography has been established as a three-dimensional (3D) imaging method for studying the hydraulic function of wooden plants. However, this X-ray imaging method can barely reach the resolution needed to see the minute structures (e.g. pit membrane). To complement the xylem structure with 3D views at the nanoscale level, X-ray near-field nano-holotomography (NFH) was applied to analyze the wood species Pinus sylvestris and Fagus sylvatica. The demanded small specimens required focused ion beam (FIB) application. The FIB milling, however, influenced the image quality through gallium implantation on the cell-wall surfaces. The measurements indicated that NFH is appropriate for imaging wood at nanometric resolution. With a 26 nm voxel pitch, the structure of the cell-wall surface in Pinus sylvestris could be visualized in genuine detail. In wood of Fagus sylvatica, the structure of a pit pair, including the pit membrane, between two neighboring fibrous cells could be traced tomographically.

Sci Rep 11, 4574 (2021)

Koddenberg, T., Greving, I., Hagemann, J. et al.
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  • 1 min read

The low-barrier methyl internal rotation in the rotational spectrum of 3-methylphenylacetylene

The rotational spectrum of 3-methylphenylacetylene has been recorded in the 2–8 GHz region using a chirped-pulse broadband microwave spectrometer. Torsion-rotation transition splittings are observed from a tunneling motion along the methyl internal rotation axis. The XIAM program was used to characterize the splitting, yielding an internal rotation barrier, , of cm−1. While this barrier is considered low, fits of A-state only transitions yield a quality, rigid-rotor fit, and are compared to the combined A/E fits. Computationally predicted barriers are estimated between 14.4 and 28.9 cm−1.

Journal of Molecular Structure, Volume 1213, 2020

Sérgio R. Domingos, Cristóbal Pérez, Mark D. Marshall, Helen O. Leung, Melanie Schnell
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  • 1 min read

Exploring key ionic interactions for magnesium degradation in simulated body fluid

We have studied the degradation of pure magnesium wire in simulated body fluid and its subsets under physiological conditions to enable the prediction of the degradation rate based on the medium's ionic composition. To this end, micro-computed tomography and scanning electron microscopy with energy-dispersive X-ray spectroscopy were used, followed by a tree regression analysis. A non-linear relationship was found between degradation rate and the precipitation of calcium salts. The mean absolute error for predicting the degradation rate was 1.35 mm/yr. This comparatively high value indicates that ionic interactions were exceedingly complex or that an unknown parameter determining the degradation may exist.

Corrosion Science Volume 182, 15 April 2021, 109272

Berit Zeller-Plumhoff, Melissa Gile, Melissa Priebe, Hanna Slominska, Benjamin Boll, BjörnWiese, TimWürger, RegineWillumeit-Römer, Robert Horst Meißner
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The New SARS-CoV-2 Strain Shows a Stronger Binding Affinity to ACE2 Due to N501Y Mutation

SARS-CoV-2 is a global challenge due to its ability to spread much faster than SARS-CoV, which was attributed to the mutations in the receptor binding domain (RBD). These mutations enhanced the electrostatic interactions. Recently, a new strain was reported in the UK that includes a mutation (N501Y) in the RBD, that possibly increases the infection rate. Using Molecular Dynamics simulations (MD) and Monte Carlo (MC) sampling, we showed that the N501 mutation enhances the electrostatic interactions due to the formation of a strong hydrogen bond between SARS-CoV-2-T500 and ACE2-D355 near the mutation site. In addition, we observed that the electrostatic interactions between the SARS-CoV-2 and ACE2 in the wild type and the mutant are dominated by salt-bridges formed between SARS-CoV-2-K417 and ACE2-D30, SARS-CoV-2-K458, ACE2-E23, and SARS-CoV-2-R403 and ACE2-E37. These interactions contributed more than 40 % of the total binding energies.

https://arxiv.org/abs/2101.01791

Fedaa Ali, Amal Kasry, Muhamed Amin
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  • 1 min read

Inhibition of SARS-CoV-2 main protease by allosteric drug-binding

The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous health problems and economical challenges for mankind. To date, no effective drug is available to directly treat the disease and prevent virus spreading. In a search for a drug against COVID-19, we have performed a massive X-ray crystallographic screen of two repurposing drug libraries against the SARS-CoV-2 main protease (Mpro), which is essential for the virus replication and, thus, a potent drug target. In contrast to commonly applied X-ray fragment screening experiments with molecules of low complexity, our screen tested already approved drugs and drugs in clinical trials. From the three-dimensional protein structures, we identified 37 compounds binding to Mpro. In subsequent cell-based viral reduction assays, one peptidomimetic and five non-peptidic compounds showed antiviral activity at non-toxic concentrations. We identified two allosteric binding sites representing attractive targets for drug development against SARS-CoV-2.

https://doi.org/10.1101/2020.11.12.378422

Sebastian Günther and many more