Some of the challenges and successes associated with density functional theory (DFT) are examined. DFT chemistry is linked to a number of areas, including geometries, hydrogen bonding and ...thermochemistry.
Density functional theory of electronic structure is widely and successfully applied in simulations throughout engineering and sciences. However, for many predicted properties, there are spectacular ...failures that can be traced to the delocalization error and static correlation error of commonly used approximations. These errors can be characterized and understood through the perspective of fractional charges and fractional spins introduced recently. Reducing these errors will open new frontiers for applications of density functional theory.
Earth is flooded with plastics and the need for sustainable recycling strategies for polymers has become increasingly urgent. Enzyme‐based hydrolysis of post‐consumer plastic is an emerging strategy ...for closed‐loop recycling of polyethylene terephthalate (PET). The polyester hydrolase PHL7, isolated from a compost metagenome, completely hydrolyzes amorphous PET films, releasing 91 mg of terephthalic acid per hour and mg of enzyme. Vertical scanning interferometry shows degradation rates of the PET film of 6.8 μm h−1. Structural analysis indicates the importance of leucine at position 210 for the extraordinarily high PET‐hydrolyzing activity of PHL7. Within 24 h, 0.6 mgenzyme gPET−1 completely degrades post‐consumer thermoform PET packaging in an aqueous buffer at 70 °C without any energy‐intensive pretreatments. Terephthalic acid recovered from the enzymatic hydrolysate is then used to synthesize virgin PET, demonstrating the potential of polyester hydrolases as catalysts in sustainable PET recycling processes with a low carbon footprint.
Tread lightly: A highly efficient polyester hydrolase derived from plant compost metagenomes rapidly degrades amorphous polyethylene terephthalate (PET) at 70 °C. The direct hydrolysis of thermoform PET packaging flakes and the conversion of the recovered terephthalic acid into virgin PET demonstrate the potential of biocatalysis in plastic recycling processes with a low carbon footprint.
Revealing Noncovalent Interactions Johnson, Erin R; Keinan, Shahar; Mori-Sánchez, Paula ...
Journal of the American Chemical Society,
05/2010, Letnik:
132, Številka:
18
Journal Article
Recenzirano
Odprti dostop
Molecular structure does not easily identify the intricate noncovalent interactions that govern many areas of biology and chemistry, including design of new materials and drugs. We develop an ...approach to detect noncovalent interactions in real space, based on the electron density and its derivatives. Our approach reveals the underlying chemistry that compliments the covalent structure. It provides a rich representation of van der Waals interactions, hydrogen bonds, and steric repulsion in small molecules, molecular complexes, and solids. Most importantly, the method, requiring only knowledge of the atomic coordinates, is efficient and applicable to large systems, such as proteins or DNA. Across these applications, a view of nonbonded interactions emerges as continuous surfaces rather than close contacts between atom pairs, offering rich insight into the design of new and improved ligands.
Owing to the lack of genetic animal models that adequately recreate key clinical characteristics of cirrhosis, the molecular pathogenesis of cirrhosis has been poorly characterized, and treatments ...remain limited. Hence, we aimed to better elucidate the pathological mechanisms of cirrhosis using a novel murine model.
We report on the first murine genetic model mimicking human cirrhosis induced by hepatocyte-specific elimination of microspherule protein 1 (MCRS1), a member of non-specific lethal (NSL) and INO80 chromatin-modifier complexes. Using this genetic tool with other mouse models, cell culture and human samples, combined with quantitative proteomics, single nuclei/cell RNA sequencing and chromatin immunoprecipitation assays, we investigated mechanisms of cirrhosis.
MCRS1 loss in mouse hepatocytes modulates the expression of bile acid (BA) transporters – with a pronounced downregulation of Na+-taurocholate cotransporting polypeptide (NTCP) – concentrating BAs in sinusoids and thereby activating hepatic stellate cells (HSCs) via the farnesoid X receptor (FXR), which is predominantly expressed in human and mouse HSCs. Consistently, re-expression of NTCP in mice reduces cirrhosis, and genetic ablation of FXR in HSCs suppresses fibrotic marks in mice and in vitro cell culture. Mechanistically, deletion of a putative SANT domain from MCRS1 evicts histone deacetylase 1 from its histone H3 anchoring sites, increasing histone acetylation of BA transporter genes, modulating their expression and perturbing BA flow. Accordingly, human cirrhosis displays decreased nuclear MCRS1 and NTCP expression.
Our data reveal a previously unrecognized function of MCRS1 as a critical histone acetylation regulator, maintaining gene expression and liver homeostasis. MCRS1 loss induces acetylation of BA transporter genes, perturbation of BA flow, and consequently, FXR activation in HSCs. This axis represents a central and universal signaling event in cirrhosis, which has significant implications for cirrhosis treatment.
By genetic ablation of MCRS1 in mouse hepatocytes, we generate the first genetic mouse model of cirrhosis that recapitulates human features. Herein, we demonstrate that the activation of the bile acid/FXR axis in liver fibroblasts is key in cirrhosis development.
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•MCRS1 loss in hepatocytes deregulates the expression of BA transporters, causing perturbation of BA flow and cirrhosis.•Re-expression of the BA transporter NTCP in MCRS1-depleted hepatocytes restores the BA flow and prevents cirrhosis.•Accumulation of BAs in liver sinusoids activates liver fibroblasts via FXR leading to fibrosis.•MCRS1 loss increases histone acetylation of BA transporter genes, altering their expression levels.•MCRS1 and NTCP expression correlates with fibrotic marks in human cirrhosis samples.
We present reverberation mapping (RM) results for 17 high-redshift, high-luminosity quasars with good-quality R-band and emission-line light curves. We are able to measure statistically significant ...lags for Ly (11 objects), Si iv (5 objects), C iv (11 objects), and C iii (2 objects). Using our results and previous lag determinations taken from the literature, we present an updated C iv radius-luminosity relation and provide for the first time radius-luminosity relations for Ly , Si iv, and C iii. While in all cases the slopes of the correlations are statistically significant, the zero points are poorly constrained because of the lack of data at the low-luminosity end. We find that the emissivity-weighted distances from the central source of the Ly , Si iv, and C iii line-emitting regions are all similar, which corresponds to about half that of the Hβ region. We also find that 3/17 of our sources show an unexpected behavior in some emission lines, two in the Ly light curve and one in the Si iv light curve, in that they do not seem to follow the variability of the UV continuum. Finally, we compute RM black hole (BH) masses for those quasars with highly significant lag measurements and compare them with C iv single-epoch (SE) mass determinations. We find that the RM-based BH mass determinations seem smaller than those found using SE calibrations.
The band-gap problem and other systematic failures of approximate exchange-correlation functionals are explained from an analysis of total energy for fractional charges. The deviation from the ...correct intrinsic linear behavior in finite systems leads to delocalization and localization errors in large and bulk systems. Functionals whose energy is convex for fractional charges such as the local density approximation display an incorrect apparent linearity in the bulk limit, due to the delocalization error. Concave functionals also have an incorrect apparent linearity in the bulk calculation, due to the localization error and imposed symmetry. This resolves an apparent paradox and identifies the physical nature of the error to be addressed to obtain accurate band gaps from density functional theory.
In this work, we examine the fractional charge behaviors of doubly hybrid (DH) functionals. By plotting the ground-state energies E and energy derivatives for atoms and molecules with fractional ...electron numbers N, we directly quantify the delocalization errors of some representative DH functionals such as B2PLYP, XYG3, and XYGJ-OS. Numerical assessments on ionization potentials (IPs), electron affinities (EAs), and fundamental gaps, from either integer number calculations or energy derivative calculations, are provided. It is shown that the XYG3 type of DH functionals gives good agreement between their energy derivatives and the experimental IPs, EAs, and gaps, as expected from their nearly straight line fractional charge behaviors.
A stochastic minimization method for a real-space wave function, Ψ(r 1, r 2...r n ), constrained to a chosen density, ρ(r), is developed. It enables the explicit calculation of the Levy constrained ...search, Fρ = minΨ→ρ⟨Ψ|T̂ + V̂ ee |Ψ⟩, which gives the exact functional of density functional theory. This general method is illustrated in the evaluation of Fρ for densities in one dimension with a soft-Coulomb interaction. Additionally, procedures are given to determine the first and second functional derivatives, δF/δρ(r) and δ2 F/δρ(r)δρ(r′). For a chosen external potential, v(r), the functional and its derivatives are used in minimizations over densities to give the exact energy, E v , without needing to solve the Schrödinger equation.
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