Molecular mechanism by which high temperature and RecBCD synergistically lower strand-separation barriers and promote destabilization of representative efflux-pump ARG fragments (macB/tetA) during hyperthermophilic composting.

Identifying potential relationships between air pollutants and neutrophil extracellular traps formation in metabolic dysfunction-associated fatty liver disease by integrating computational toxicology and multi-omics data.

An integrated in silico and multi-omics workflow identifies novel microbiota-derived umami peptides and elucidates T1R1/T1R3 binding mechanisms.

Myosin-bound glycyrrhizic acid and liquiritin from Glycyrrhiza uralensis Fisch. attenuate thermal polycyclic aromatic hydrocarbon formation: spectroscopic and computational mechanistic insights.

Synthesis, biological evaluation, and mechanism investigation of multisubstituted quinazoline analogues as prospective inhibitors of KRAS G12D.

Low kinetic perturbation by the rapidly advancing ice-water interface suppresses Na+/Cl- induced myofibrillar protein network assembly.

Click chemistry synthesis of triazole-grafted quinazolinones as new multi-panel anticancer agents: mechanistic insights into apoptosis and cell cycle arrest in colorectal cancer.

The heterogeneous reactions of nitrophenols and their impact on HONO generation: The influence of mineral dusts.

A green self-assembled hydrogel developed from glycyrrhizic acid and berberine for shelf-life extension and flavor quality preservation of strawberry fruits.

Identification of a novel patulin degrading enzyme from Wickerhamomyces anomalus XL1 and its application in apple juice.

Thermal runaway of organic peroxides in chemical production poses a persistent and severe challenge in the field of energy and safety. The ambiguous decomposition mechanism of peroxypropionic acid (PPA), a typical and unstable peroxide, hinders effective risk prevention and control. This study employs a multiscale computational approach integrating reactive molecular dynamics (ReaxFF MD) and density functional theory (DFT) to unravel, for the first time, the complete reaction network and energy evolution pathway of a PPA mixture under thermal runaway conditions at the atomic scale. Simulation results reveal that its decomposition follows a typical free radical chain reaction mechanism, progressing through three self-accelerating stages: initial homolytic initiation, a vigorous exothermic propagation dominated by hydrogen abstraction reactions, and final secondary decomposition of products driven by accumulated heat. DFT calculations precisely quantified the activation energy barriers and reaction enthalpies of key elementary steps, identifying the rate-determining steps that drive thermal runaway. Adiabatic experiments validated the intense exothermic characteristics predicted by the simulations. This work clarifies the microscopic driving forces behind PPA thermal runaway, providing crucial molecular-level insights and thermodynamic data for designing safer operational protocols and developing efficient inhibitors at an industrial scale.

Hydrazine is a highly hazardous chemical and can be present in the atmosphere due to its usage in rocket fuels and propellant mixtures. Ice particles, present in polar stratospheric clouds, are common components of the natural atmosphere and can adsorb small organic molecules, such as hydrazine. We investigate the (0001) surface of hexagonal ice, acting as a phase boundary for the adsorption of hydrazine using density functional theory (DFT). Different types of position of hydrazine monomers and dimers on the ice surface were considered. We analyze the energetic and structural properties of these adsorbates utilizing static DFT calculations and Car-Parrinello molecular dynamics simulations. We study the interplay between molecule-molecule (N2H4-N2H4) and molecule-substrate (N2H4-ice surface) interactions, in particular self-aggregation of hydrazine in H-bonded complexes. Molecular dynamics simulations enable to study the dynamics of the system, namely, reaction pathways for molecular rearrangements of N2H4 monomers and dimers and the possible interconversion between the two hydrazine enantiomers on the ice (0001) surface.

Isoliquiritigenin ameliorates Pseudomonas aeruginosa-induced acute lung injury through inhibiting lung epithelial cell ferroptosis via PPARγ/Nrf2/GPX4 axis.

To investigate the gene sequence, protein structure, and impact of the variant on glycosyltransferase B (GTB) structural stability in a patient with a ABO*Bw.28 subtype. A 33-year-old man with mixed hemorrhoids, confirmed as ABO*Bw.28 by genetic sequencing at the Second Affiliated Hospital of Wenzhou Medical University on December 8, 2022 was selected as study subject. ABO phenotyping was performed using tube test, microcolumn gel assay, and absorption-elution test. Genetic testing was conducted by PCR-direct sequencing, with haplotype confirmation by TOPO-TA cloning. Homology modeling was performed using PyMOL, and 100 ns molecular dynamics simulations of wild-type and mutant GTB were conducted using GROMACS to assess root-mean-square deviation (RMSD), radius of gyration (Rg), solventaccessible surface area (SASA), hydrogen bonds, and binding free energy. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2021-K-289-01). Serological tests revealed characteristics of Bw subtype. ABO gene sequencing identified a c.541T>C variant in exon 7, resulting in p.Trp181Arg substitution. Haplotype analysis confirmed presence of the ABO*Bw.28 allele. Molecular modeling showed that the Trp181Arg substitution largely abolished hydrophobic interactions with the UDP-galactose (UDP-Gal) ligand and reduced the number of active site hydrogen bonds (wildtype: 2 ~ 8; variant: 1 ~ 6). Molecular dynamics simulation suggested increased binding free energy from 11.586 kcal/mol (wild type) to 4.680 kcal/mol (variant), indicating a disrupted local hydrogen bond network and reduced conformational stability and substrate binding affinity. This study has identified a case with a c.541T>C (p.Trp181Arg) ABO variant. The variant may disrupt the hydrophobic interactions and local hydrogen bond network, reducing GTB catalytic domain stability and B antigen expression, thus providing a molecular basis for the Bw.28 subtype.

Molecular mechanisms governing antibiotic transport in spider silk-riboflavin hydrogels.

Structural and functional insights into an anticancer peptide candidate derived from the EP400NL C-terminal domain.

The integration time step is a critical determinant of performance in molecular dynamics simulations, governing the trade-off between speed and fidelity. Although 2fs remains the standard in atomistic biomolecular simulations, the push for performance has popularized a 4fs time step with hydrogen mass repartitioning, often combined with multiple time stepping or mass rescaling. However, it is often unclear whether a chosen protocol is overly aggressive, as the apparent numerical stability of a trajectory can mask underlying thermodynamic inaccuracies. Increasing the time step will exacerbate systematic discretization errors, inherent to all numerical integration algorithms. In the widely used Verlet family of integrators, these errors manifest as O(Δt2) deviations in thermodynamic observables such as potential energy and volume, and for common Langevin splitting schemes, even temperature. We demonstrate that these deviations follow a simple, linear thermodynamic model, allowing for their rigorous removal by extrapolation to the zero time step limit. In turn, the time-step dependence provides us with estimates of the system heat capacity, compressibility, and thermal expansion coefficient. This framework allows us to construct consistent probability distributions of energy and volume across thermodynamic states, effectively recovering Boltzmann-consistent statistics at a target condition independent of time step. These considerations are particularly important for enhanced sampling methods, such as replica exchange and umbrella sampling, which rely on rigorous Boltzmann sampling and require accurate energies and temperatures for valid replica exchange probabilities and statistical reweighting.

Meroterpenoids from Rhododendron dauricum and the self-assembly driven antibacterial enhancement of grifolin.

Discovery of garlic-derived peptides as natural DPP4 inhibitors: An integrated computational, network pharmacology, and in situ evaluation approach.

Gating by voltage-dependent anion channels (VDAC) regulates mitochondrial metabolite flux, yet the structural mechanism underlying the open-to-closed transition remains unresolved. Here, we combine atomistic molecular dynamics (MD) simulations with double electron-electron resonance (DEER), using hydrostatic pressure as a reversible thermodynamic perturbation to shift conformational equilibria and stabilize low-population states. MD simulations reveal localized intrinsic flexibility within β-strands β1-β5 and β19, as well as in cytosolic loops connecting β6-β7 and β8-β9. High-pressure DEER measurements in lipid nanodiscs corroborate these predictions, identifying reversible, pressure-dependent distance changes within the pore lumen consistent with asymmetric deformation of the β-barrel. DEER-informed analysis of unbiased MD trajectories reveals an elliptical β-barrel conformation aligned parallel to the N-terminal helix that corresponds to the pressure-stabilized experimental state. ATP permeation simulations identify a free-energy barrier to metabolite translocation in this elliptical geometry, whereas diffusion through the circular open state is energetically favorable. These findings indicate that the elliptical conformation represents a transient gating-competent state rather than a fully closed channel. Together, our results support a gating mechanism driven by reversible β-barrel deformation and establish pressure-perturbed DEER integrated with MD as a general strategy for capturing transient, functionally relevant conformations of membrane channels.