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Recent analyses of public microbial genomes have found over a million biosynthetic gene clusters, the natural products of the majority of which remain unknown. Additionally, GNPS harbors billions of mass spectra of natural products without known structures and biosynthetic genes. We bridge the gap between large-scale genome mining and mass spectral datasets for natural product discovery by developing HypoRiPPAtlas, an Atlas of hypothetical natural product structures, which is ready-to-use for in silico database search of tandem mass spectra. HypoRiPPAtlas is constructed by mining genomes using seq2ripp, a machine-learning tool for the prediction of ribosomally synthesized and post-translationally modified peptides (RiPPs). In HypoRiPPAtlas, we identify RiPPs in microbes and plants. HypoRiPPAtlas could be extended to other natural product classes in the future by implementing corresponding biosynthetic logic. This study paves the way for large-scale explorations of biosynthetic pathways and chemical structures of microbial and plant RiPP classes.

 

This work reports a method of producing flexible cobalt nanowires (NWs) directly from the chemical conversion of bulk precursors at room temperature. Chemical reduction of Li 6 CoCl 8 produces a nanocomposite of Co and LiCl, of which the salt is subsequently removed. The dilute concentration of Co in the precursor combined with the anisotropic crystal structure of the hcp phase leads to 1D growth in the absence of any templates or additives. The Co NWs are shown to have high saturation magnetization (130.6 emu g −1 ). Our understanding of the NW formation mechanism points to new directions of scalable nanostructure generation. 

Although ammonia is a widely used interstellar thermometer, the estimation of its rotational and kinetic temperatures can be affected by the blended hyperfine components (HFCs). We have developed a new recipe, referred to as the hyperfine group ratio (HFGR), which utilizes only direct observables, namely the intensity ratios between the grouped HFCs. As tested on the model spectra, the empirical formulae in the HFGR can derive the rotational temperature (Trot) from the HFC group ratios in an unambiguous manner. We compared the HFGR with two other classical methods, intensity ratio and hyperfine fitting, based on both simulated spectra and real data. The HFGR has three major improvements. First, it does not require modelling the HFC or fitting the line profiles, so it is more robust against the effect of HFC blending. Second, the simulation-enabled empirical formulae are much faster than fitting the spectra over the parameter space, so both computer time and human time can be saved. Third, the statistical uncertainty of the temperature ΔTrot as a function of the signal-to-noise ratio (S/N) is a natural product of the HFGR recipe. The internal error of the HFGR is ΔTrot ≤ 0.5 K over a broad parameter space of rotational temperature (10-60 K), linewidth (0.3-4 km s-1) and optical depth (0-5). When there is spectral noise, the HFGR can also maintain a reasonable uncertainty level at ΔTrot ≤ 1.0 K when S/N > 4. 

As the core component of the adherens junction in cell–cell adhesion, the cadherin–catenin complex transduces mechanical tension between neighboring cells. Structural studies have shown that the cadherin–catenin complex exists as an ensemble of flexible conformations, with the actin-binding domain (ABD) of α-catenin adopting a variety of configurations. Here, we have determined the nanoscale protein domain dynamics of the cadherin–catenin complex using neutron spin echo spectroscopy (NSE), selective deuteration, and theoretical physics analyses. NSE reveals that, in the cadherin–catenin complex, the motion of the entire ABD becomes activated on nanosecond to submicrosecond timescales. By contrast, in the α-catenin homodimer, only the smaller disordered C-terminal tail of ABD is moving. Molecular dynamics (MD) simulations also show increased mobility of ABD in the cadherin–catenin complex, compared to the α-catenin homodimer. Biased MD simulations further reveal that the applied external forces promote the transition of ABD in the cadherin–catenin complex from an ensemble of diverse conformational states to specific states that resemble the actin-bound structure. The activated motion and an ensemble of flexible configurations of the mechanosensory ABD suggest the formation of an entropic trap in the cadherin–catenin complex, serving as negative allosteric regulation that impedes the complex from binding to actin under zero force. Mechanical tension facilitates the reduction in dynamics and narrows the conformational ensemble of ABD to specific configurations that are well suited to bind F-actin. Our results provide a protein dynamics and entropic explanation for the observed force-sensitive binding behavior of a mechanosensitive protein complex.