Solid-State NMR Validation of OPLS4: Structure of PC-Lipid Bilayers and Its Modulation by Dehydration.

Atomistic molecular dynamics (MD) simulations are a much-used tool for investigating the structure and dynamics of biomembranes with atomic resolution. The validity of the representations obtained is determined by the accuracy and realism of the MD model (force field). Here, we evaluated the proprietary OPLS4 force field of Schrödinger, Inc.

Overlay databank unlocks data-driven analyses of biomolecules for all.

Tools based on artificial intelligence (AI) are currently revolutionising many fields, yet their applications are often limited by the lack of suitable training data in programmatically accessible format. Here we propose an effective solution to make data scattered in various locations and formats accessible for data-driven and machine learning applications using the overlay databank format. To demonstrate the practical relevance of such approach, we present the NMRlipids Databank-a community-driven, open-for-all database featuring programmatic access to quality-evaluated atom-resolution molecular dynamics simulations of cellular membranes.

Dataset on the proteomic response during ferroptosis induction via tamoxifen induced GPX4 KO in mouse embryonic fibroblasts.

Ferroptosis is a type of programmed cell death distinct from apoptosis and necroptosis that plays an essential role in pathophysiological conditions such as neurodegenerative diseases and tumorigenesis. Massive lipid oxidation in an iron-dependent manner is a hallmark of ferroptosis.This modality of cell death is also characterized by perturbation of several metabolic pathways, predominantly fatty acid metabolism, thiol metabolism, iron homeostasis and the mevalonate pathway.

Voluntary wheel exercise training affects locomotor muscle, but not the diaphragm in the rat.

Functional tests and training regimens intensity-controlled by an individual are used in sport practice, clinical rehabilitation, and space medicine. The model of voluntary wheel running in rats can be used to explore molecular mechanisms of such training regimens in humans. Respiratory and locomotor muscles demonstrate diverse adaptations to treadmill exercise, but the effects of voluntary exercise training on these muscle types have not been compared yet.

Targeted search for scaling genes reveals matrixmetalloproteinase 3 as a scaler of the dorsal-ventral pattern in Xenopus laevis embryos.

How embryos scale patterning according to size is still not fully understood. Through in silico screening and analysis of reaction-diffusion systems that could be responsible for scaling, we predicted the existence of genes whose expression is sensitive to embryo size and which regulate the scaling of embryonic patterning. To find these scalers, we identified genes with strongly altered expression in half-size Xenopus laevis embryos compared with full-size siblings at the gastrula stage.

Inhomogeneity of polylysine adsorption layers on lipid membranes revealed by theoretical analysis of electrokinetic data and molecular dynamics simulations.

The adsorption of large polycations on a charged lipid membrane is qualitatively different from the small inorganic cations, which almost uniformly populate the membrane surface. We assume that the polycationic adsorption layer might be laterally inhomogeneous starting from a certain polymer length, and this effect can be more visible for membranes with low anionic lipid content. To study systems with inhomogeneous adsorption layers, we carried out electrokinetic measurements of mobility of liposomes containing anionic and neutral phospholipids in the presence of polylysine molecules.

Colloidal graphene oxide enhances the activity of a lipase and protects it from oxidative damage: Insights from physicochemical and molecular dynamics investigations.

Physical adsorption of lipase from Thermomyces lanuginosus onto single-layer sheets of graphene oxide (GO) was studied using the response surface methodology to evaluate the physicochemical factors - temperature, pH, ionic strength, and concentration - affecting the enzymatic activity and the immobilization efficiency. The immobilization efficiency and the activity of the enzyme were inversely proportional to each other. Specifically, higher pH values increased the immobilization efficacy, but produced changes in the aggregation state and secondary structure of the enzyme, thus decreasing its activity.

MitoCLox: A Novel Mitochondria-Targeted Fluorescent Probe for Tracing Lipid Peroxidation.

Peroxidation of cardiolipin (CL) in the inner mitochondrial membrane plays a key role in the development of various pathologies and, probably, aging. The four fatty acid tails of CL are usually polyunsaturated, which makes CL particularly sensitive to peroxidation. Peroxidation of CL is involved in the initiation of apoptosis, as well as in some other important cellular signaling chains.

Bioinformatics Screening of Genes Specific for Well-Regenerating Vertebrates Reveals c-answer, a Regulator of Brain Development and Regeneration.

The molecular basis of higher regenerative capacity of cold-blooded animals comparing to warm-blooded ones is poorly understood. Although this difference in regenerative capacities is commonly thought to be a result of restructuring of the same regulatory gene network, we hypothesized that it may be due to loss of some genes essential for regeneration. We describe here a bioinformatic method that allowed us to identify such genes.

Explicit measurement of the endotoxin adsorption efficiency detects non-Langmuir behavior at low concentrations.

Lipopolysaccharides (LPS) are the Gram-negative bacteria cell wall components capable to induce the system inflammatory response even at picomolar concentrations. LPS detection at these concentrations is necessary to develop new sorbents for the efficient purification of the biological fluids. LAL-test widely used for LPS concentration estimation is based on the LPS biological activity measurement and thus may depend on the LPS concentration in a non-linear way.

Comprehensive Study of the Liquid Expanded-Liquid Condensed Phase Transition in 1,2-Dimyristoyl--glycero-3-phospho-l-serine Monolayers: Surface Pressure, Volta Potential, X-ray Reflectivity, and Molecular Dynamics Modeling.

An integrated approach is applied to reveal fine changes in the surface-normal structure of 1,2-dimyristoyl--glycero-3-phospho-l-serine (DMPS) monolayers at the air-lipid-water interface occurring in a liquid expanded (LE)-liquid condensed (LC) transition. The combination of the Langmuir monolayer technique, X-ray reflectometry, and molecular dynamics (MD) modeling provides new insight into the molecular nature of electrostatic phenomena in different stages of lipid compression. A homemade setup with a laboratory X-ray source (λ = 1.

Molecular Dynamics Modeling of the Interaction of Cationic Fluorescent Lipid Peroxidation-Sensitive Probes with the Mitochondrial Membrane.

Cardiolipin (CL) plays a central role in lipid peroxidation (LPO) of the mitochondrial inner membrane due to higher content of unsaturated fatty acids in CL in comparison with the other phospholipids. CL oxidation plays an important role in the regulation of various intracellular signaling pathways and its excessive oxidation contributes to the development of various pathologies and, possibly, participates in the aging process. Mitochondria-targeted antioxidants containing triphenylphosphonium (TPP) effectively protect CL from oxidation.

Impact of the chemical structure on amphiphilic properties of sugar-based surfactants: A literature overview.

In this review, structure-property trends are systematically analyzed for four amphiphilic properties of sugar-based surfactants: critical micelle concentration (CMC), its associated surface tension (γ), efficiency (pC) and Krafft temperature (T). First, the impact on amphiphilic properties of the alkyl chain size and the presence of branching and/or unsaturation is investigated. Then, various polar head parameters are explored, such as the degree of polymerization of the sugar unit (mono- or oligosaccharides), the chemical nature of the linker and the sugar configuration.

Agr2-interacting Prod1-like protein Tfp4 from Xenopus laevis is necessary for early forebrain and eye development as well as for the tadpole appendage regeneration.

The Agr family genes, Ag1, Agr2, and Agr3, encode for the thioredoxin domain containing secreted proteins and are specific only for vertebrates. These proteins are attracting increasing attention due to their involvement in many physiological and pathological processes, including exocrine secretion, cancer, regeneration of the body appendages, and the early brain development. At the same time, the mode by which Agrs regulate intracellular processes are poorly understood.

Efficacy of Combined Regional Inductive Moderate Hyperthermia and Chemotherapy in Patients With Multiple Liver Metastases From Breast Cancer.

Purpose: Regional inductive moderate hyperthermia in combination with chemotherapy can improve the therapeutic efficacy in patients with breast cancer with multiple liver metastases.

Methods: The study included 103 patients with breast cancer with multiple liver metastases: 53 patients (main group) who received a combined chemotherapy (TC drug combination) and regional inductive moderate hyperthermia treatment and 50 patients (control group) who received chemotherapy (TC drug combination) alone. Regional inductive moderate hyperthermia exploited electromagnetic fields with an operating frequency of 27.

Molecular Mechanism of Uptake of Cationic Photoantimicrobial Phthalocyanine across Bacterial Membranes Revealed by Molecular Dynamics Simulations.

Phthalocyanines are aromatic macrocyclic compounds, which are structurally related to porphyrins. In clinical practice, phthalocyanines are used in fluorescence imaging and photodynamic therapy of cancer and noncancer lesions. Certain forms of the substituted polycationic metallophthalocyanines have been previously shown to be active in photodynamic inactivation of both Gram-negative and Gram-positive bacteria; one of them is zinc octakis(cholinyl)phthalocyanine (ZnPcChol).

Morphogene adsorption as a Turing instability regulator: Theoretical analysis and possible applications in multicellular embryonic systems.

The Turing instability in the reaction-diffusion system is a widely recognized mechanism of the morphogen gradient self-organization during the embryonic development. One of the essential conditions for such self-organization is sharp difference in the diffusion rates of the reacting substances (morphogens). In classical models this condition is satisfied only for significantly different values of diffusion coefficients which cannot hold for morphogens of similar molecular size.

What Can We Learn about Cholesterol's Transmembrane Distribution Based on Cholesterol-Induced Changes in Membrane Dipole Potential?

Cholesterol is abundant in the plasma membranes of animal cells and is known to regulate a variety of membrane properties. Despite decades of research, the transmembrane distribution of cholesterol is still a matter of debate. Here we consider this outstanding issue through atomistic simulations of asymmetric lipid membranes, whose composition is largely consistent with eukaryotic plasma membranes.

[Hox Genes and Animal Regeneration].

The concept of regeneration is intimately associated with ideas about positional information, that is, the distribution of various signals prescribing cells their location in an embryo or an adult organism. Hox genes are perfect candidates for the role of factors creating positional information. Their main function is thought to be regionalization of the embryo and the determination of the anterior/posterior (A/P) axis of the bilaterian body according to the rules of temporal and spatial colinearity.

Conformational Dynamics of the Single Lipopolysaccharide O-Antigen in Solution.

The O-antigen is the most variable and highly immunogenic part of the lipopolysaccharide molecule that covers the surface of Gram-negative bacteria and makes up the first line of cellular defense. To provide insight into the details of the O-antigen arrangement on the membrane surface, we simulated its behavior in solution by molecular dynamics. We developed the energetically favorable O-antigen conformation by analyzing free-energy distributions for its disaccharide fragments.

Atomic-Scale Molecular Dynamics Simulations of DNA-Polycation Complexes: Two Distinct Binding Patterns.

Synthetic cationic polymers represent a promising class of delivery vectors for gene therapy. Here, we employ atomistic molecular dynamics simulations to gain insight into the structure and properties of complexes of DNA with four linear polycations: polyethylenimine (PEI), poly-l-lysine (PLL), polyvinylamine (PVA), and polyallylamine (PAA). These polycations differ in their polymer geometries, protonation states, and hydrophobicities of their backbone chains.