Co-evolutionary distance predictions contain flexibility information.

MOTIVATION: Co-evolution analysis can be used to accurately predict residue-residue contacts from multiple sequence alignments. The introduction of machine-learning techniques has enabled substantial improvements in precision and a shift from predicting binary contacts to predict distances between pairs of residues. These developments have significantly improved the accuracy of de novo prediction of static protein structures. With AlphaFold2 lifting the accuracy of some predicted protein models close to experimental levels, structure prediction research will move on to other challenges. One of those areas is the prediction of more than one conformation of a protein. Here, we examine the potential of residue-residue distance predictions to be informative of protein flexibility rather than simply static structure. RESULTS: We used DMPfold to predict distance distributions for every residue pair in a set of proteins that showed both rigid and flexible behaviour. Residue pairs that were in contact in at least one reference structure were classified as rigid, flexible or neither. The predicted distance distribution of each residue pair was analysed for local maxima of probability indicating the most likely distance or distances between a pair of residues. We found that rigid residue pairs tended to have only a single local maximum in their predicted distance distributions while flexible residue pairs more often had multiple local maxima. These results suggest that the shape of predicted distance distributions contains information on the rigidity or flexibility of a protein and its constituent residues. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Searching for Axionlike Particles under Strong Gravitational Lenses.

We establish strong gravitational lens systems as robust probes of axionlike particles (ALPs)-a candidate for dark matter. A tiny interaction of photons with ALPs induces birefringence. Multiple images of gravitationally lensed polarized objects allow measurement of differential birefringence, alleviating systematics and astrophysical dependencies. We apply this novel method to the lens system CLASS B1152+199 and constrain the ALP-photon coupling ≤9.2×10^{-11} to 7.7×10^{-8} GeV^{-1} (95% C.L.) for an ALP mass between 3.6×10^{-21} and 4.6×10^{-18} eV. A larger sample will improve the constraints.

Modeling conformational flexibility of kinases in inactive states.

Kinase structures in the inactive "DFG-out" state provide a wealth of druggable binding site variants. The conformational plasticity of this state can be mainly described by different conformations of binding site-forming elements such as DFG motif, A-loop, P-loop, and αC-helix. Compared to DFG-in structures, DFG-out structures are largely underrepresented in the Protein Data Bank (PDB). Thus, structure-based drug design efforts for DFG-out inhibitors may benefit from an efficient approach to generate an ensemble of DFG-out structures. Accordingly, the presented modeling pipeline systematically generates homology models of kinases in several DFG-out conformations based on a sophisticated creation of template structures that represent the major states of the flexible structural elements. Eighteen template classes were initially selected from all available kinase structures in the PDB and subsequently employed for modeling the entire kinome in different DFG-out variants by fusing individual structural elements to multiple chimeric template structures. Molecular dynamics simulations revealed that conformational transitions between the different DFG-out states generally do not occur within trajectories of a few hundred nanoseconds length. This underlines the benefits of the presented homology modeling pipeline to generate relevant conformations of "DFG-out" kinase structures for subsequent in silico screening or binding site analysis studies.

Cosmic QCD Epoch at Nonvanishing Lepton Asymmetry.

We investigate how a lepton asymmetry impacts the cosmic trajectory in the QCD phase diagram. We study the evolution of chemical potentials during the QCD epoch of the early Universe using susceptibilities from lattice QCD to interpolate between an ideal quark gas and an ideal hadron resonance gas. The lepton asymmetry affects the evolution of all chemical potentials. The standard cosmic trajectory is obtained assuming tiny lepton and baryon asymmetries. For larger lepton asymmetry, the charge chemical potential exceeds the baryon chemical potential before pion annihilation.

Biosynthesis of poly-3-hydroxybutyrate from grass silage by a two-stage fermentation process based on an integrated biorefinery concept.

Grass silage as a renewable feedstock for an integrated biorefinery includes nutrients and carbon sources directly available in the press juice (PJ) and in lignocellulosic saccharides from the plant framework. Here, a novel two-stage fed-batch fermentation process for biosynthesis of poly-3-hydroxybutyrate (PHB) by Cupriavidus necator DSM 531 is presented. For bacterial growth, nutrient-rich PJ was employed as a fermentation medium, without any supplements. Saccharides derived from the mechano-enzymatic hydrolysis of the press cake (PC) were subjected to a lactic acid fermentation process, before the fermentation products were fed into the polymer accumulation phase. By combination of pH-stat feeding and cell recycling, the PHB content in 22 g L-1 total-dry cells reached 39% after 32 h of cultivation. Using mimicked hydrolyzate of diluted PJ artificially supplemented with glucose and xylose, the resulting cell dry weight of 21 g L-1 contained 42% PHB.

Dataset on the structural characterization of organosolv lignin obtained from ensiled Poaceae grass and load-dependent molecular weight changes during thermoplastic processing.

This article presents experimental data of organosolv lignin from Poacea grass and structural changes after compounding and injection molding as presented in the research article "Effects of high-lignin-loading on thermal, mechanical, and morphological properties of bioplastic composites" [1]. It supplements the article with morphological (SEM), spectroscopic (31P NMR, FT-IR) and chromatographic (GPC, EA) data of the starting lignin as well as molar mass characteristics (mass average molar mass (Mw) and Polydispersity (D)) of the extracted lignin. Refer to Schwarz et al. [2] for a detailed description of the production of the organosolv residue and for further information on the raw material used for lignin extraction. The dataset is made publicly available and can be useful for extended lignin research and critical analyzes.

Comparative genomic analysis of mollicutes with and without a chaperonin system.

The GroE chaperonin system, which comprises GroEL and GroES, assists protein folding in vivo and in vitro. It is conserved in all prokaryotes except in most, but not all, members of the class of mollicutes. In Escherichia coli, about 60 proteins were found to be obligatory clients of the GroE system. Here, we describe the properties of the homologs of these GroE clients in mollicutes and the evolution of chaperonins in this class of bacteria. Comparing the properties of these homologs in mollicutes with and without chaperonins enabled us to search for features correlated with the presence of GroE. Interestingly, no sequence-based features of proteins such as average length, amino acid composition and predicted folding/disorder propensity were found to be affected by the absence of GroE. Other properties such as genome size and number of proteins were also found to not differ between mollicute species with and without GroE. Our data suggest that two clades of mollicutes re-acquired the GroE system, thereby supporting the view that gaining the system occurred polyphyletically and not monophyletically, as previously debated. Our data also suggest that there might have been three isolated cases of lateral gene transfer from specific bacterial sources. Taken together, our data indicate that loss of GroE does not involve crossing a high evolutionary barrier and can be compensated for by a small number of changes within the few dozen client proteins.

Deacidification of grass silage press juice by continuous production of acetoin from its lactate via an immobilized enzymatic reaction cascade.

An immobilized enzymatic reaction cascade was designed and optimized for the deacidification of grass silage press juice (SPJ), thus facilitating the production of bio-based chemicals. The cascade involves a three-step process using four enzymes immobilized in a Ca-alginate gel and uses lactic acid to form acetoin, a value-added product. The reaction is performed with a continuous, pH-dependent substrate feed under oxygenation. With titrated lactic acid yields of up to 91% and reaction times of ca. 6h was achieved. Using SPJ as titrant yields of 49% were obtained within 6h. In this deacidification process, with acetoin one value-added bio-based chemical is produced while simultaneously the remaining press juice can be used in applications that require a higher pH. Such, this system can be applied in a multi-product biorefinery concept to take full advantage of nutrient-rich SPJ, which is a widely available and easily storable renewable resource.

Integrated biorefinery concept for grass silage using a combination of adapted pulping methods for advanced saccharification and extraction of lignin.

An integrated refining and pulping process for ensiled biomass from permanent grassland was established on laboratory scale. The liquid phase, containing the majority of water-soluble components, including 24% of the initial dry matter (DM), was first separated by mechanical pressing. The fiber fraction was subjected to high solid load saccharification (25% DM) to enhance the lignin content in the feed for subsequent organosolvation. The saccharification enzymes were pre-selected applying experimental design approaches. Cellulose convertibility was improved by a secondary pressing step during liquefaction. Combined saccharification and organosolvation showed high degree of saccharide solubilization with recovery of 98% of the glucan and 73% of the xylan from the fiber fraction in the hydrolysates, and enabled the recovery of 41% of the grass silage lignin. The effects of the treatment were confirmed by XRD and SEM tracking of cellulose crystallinity and fiber morphology throughout the pulping procedure.

Value of H(0) in the inhomogeneous universe.

Local measurements of the Hubble expansion rate are affected by structures like galaxy clusters or voids. Here we present a fully relativistic treatment of this effect, studying how clustering modifies the mean distance- (modulus-)redshift relation and its dispersion in a standard cold dark matter universe with a cosmological constant. The best estimates of the local expansion rate stem from supernova observations at small redshifts (0.01

Large-scale suppression from stochastic inflation.

We show nonperturbatively that the power spectrum of a self-interacting scalar field in de Sitter space-time is strongly suppressed on large scales. The cutoff scale depends on the strength of the self-coupling, the number of e folds of quasi-de Sitter evolution, and its expansion rate. As a consequence, the two-point correlation function of field fluctuations is free from infrared divergencies.

Is the low-l microwave background cosmic?

The large-angle (low-l) correlations of the cosmic microwave background exhibit several statistically significant anomalies compared to the standard inflationary cosmology. We show that the quadrupole plane and the three octopole planes are far more aligned than previously thought (99.9% C.L.). Three of these planes are orthogonal to the ecliptic at 99.1% C.L., and the normals to these planes are aligned at 99.6% C.L. with the direction of the cosmological dipole and with the equinoxes. The remaining octopole plane is orthogonal to the supergalactic plane at 99.6% C.L.