Steroids and steroid-like compounds alter the ion permeability of phospholipid bilayers distinct interactions with lipids and interfacial water.

Steroids are organic compounds found in all forms of biological life. Besides their structural roles in cell membranes, steroids act as signalling molecules in various physiological processes and are used to treat inflammatory conditions. It has been hypothesised that in addition to their well-characterised genomic and non-genomic pathways, steroids exert their biological or pharmacological activities an indirect, nonreceptor-mediated membrane mechanism caused by steroid-induced changes to the physicochemical properties of cell membranes.

Predicting lipid sorting in curved membranes.

Most biological membranes are curved, and both lipids and proteins play a role in generating curvature. For any given membrane shape and composition, it is not trivial to determine whether lipids are laterally distributed in a homogeneous or inhomogeneous way, and whether the inter-leaflet distribution is symmetric or not. Here we present a simple computational tool that allows to predict the preference of any lipid type for membranes with positive vs.

Stable structures or PABP1 loading protects cellular and viral RNAs against ISG20-mediated decay.

ISG20 is an IFN-induced 3'-5' RNA exonuclease that acts as a broad antiviral factor. At present, the features that expose RNA to ISG20 remain unclear, although recent studies have pointed to the modulatory role of epitranscriptomic modifications in the susceptibility of target RNAs to ISG20. These findings raise the question as to how cellular RNAs, on which these modifications are abundant, cope with ISG20.

Daptomycin avoids drug resistance mediated by the BceAB transporter in .

Drug-resistant bacteria are a serious threat to human health as antibiotics are gradually losing their clinical efficacy. Comprehending the mechanism of action of antimicrobials and their resistance mechanisms plays a key role in developing new agents to fight antimicrobial resistance. The lipopeptide daptomycin is an antibiotic that selectively disrupts Gram-positive bacterial membranes, thereby showing slower resistance development than many classical drugs.

Assembly of a unique membrane complex in type VI secretion systems of Bacteroidota.

The type VI secretion system (T6SS) of Gram-negative bacteria inhibits competitor cells through contact-dependent translocation of toxic effector proteins. In Proteobacteria, the T6SS is anchored to the cell envelope through a megadalton-sized membrane complex (MC). However, the genomes of Bacteroidota with T6SSs appear to lack genes encoding homologs of canonical MC components.

The transport activity of the multidrug ABC transporter BmrA does not require a wide separation of the nucleotide-binding domains.

ATP-binding cassette (ABC) transporters are ubiquitous membrane proteins responsible for the translocation of a wide diversity of substrates across biological membranes. Some of them confer multidrug or antimicrobial resistance to cancer cells and pathogenic microorganisms, respectively. Despite a wealth of structural data gained in the last two decades, the molecular mechanism of these multidrug efflux pumps remains elusive, including the extent of separation between the two nucleotide-binding domains (NBDs) during the transport cycle.

Martini 3 Force Field Parameters for Protein Lipidation Post-Translational Modifications.

Protein lipidations are vital co/post-translational modifications that tether lipid tails to specific protein amino acids, allowing them to anchor to biological membranes, switch their subcellular localization, and modulate association with other proteins. Such lipidations are thus crucial for multiple biological processes including signal transduction, protein trafficking, and membrane localization and are implicated in various diseases as well. Examples of lipid-anchored proteins include the Ras family of proteins that undergo farnesylation; actin and gelsolin that are myristoylated; phospholipase D that is palmitoylated; glycosylphosphatidylinositol-anchored proteins; and others.

Multiscale simulations reveal TDP-43 molecular-level interactions driving condensation.

The RNA-binding protein TDP-43 is associated with mRNA processing and transport from the nucleus to the cytoplasm. TDP-43 localizes in the nucleus as well as accumulating in cytoplasmic condensates such as stress granules. Aggregation and formation of amyloid-like fibrils of cytoplasmic TDP-43 are hallmarks of numerous neurodegenerative diseases, most strikingly present in >90% of amyotrophic lateral sclerosis (ALS) patients.

Martini 3 Coarse-Grained Force Field for Cholesterol.

Cholesterol plays a crucial role in biomembranes by regulating various properties, such as fluidity, rigidity, permeability, and organization of lipid bilayers. The latest version of the Martini model, Martini 3, offers significant improvements in interaction balance, molecular packing, and inclusion of new bead types and sizes. However, the release of the new model resulted in the need to reparameterize many core molecules, including cholesterol.

Syntactic theory of mathematical expressions.

Mathematical expressions consist of recursive combinations of numbers, variables, and operators. According to theoretical linguists, the syntactic mechanisms of natural language also provide a basis for mathematics. To date, however, no theoretically rigorous investigation has been conducted to support such arguments.

Temporal dynamics of antibody level against Lyme disease bacteria in roe deer: Tale of a sentinel?

Changes in the risk of exposure to infectious disease agents can be tracked through variations in antibody prevalence in vertebrate host populations. However, information on the temporal dynamics of the immune status of individuals is critical. If antibody levels persist a long time after exposure to an infectious agent, they could enable the efficient detection of the past circulation of the agent; if they persist only a short time, they could provide snap shots of recent exposure of sampled hosts.

Automatic Optimization of Lipid Models in the Martini Force Field Using .

After two decades of continued development of the Martini coarse-grained force field (CG FF), further refinment of the already rather accurate Martini lipid models has become a demanding task that could benefit from integrative data-driven methods. Automatic approaches are increasingly used in the development of accurate molecular models, but they typically make use of specifically designed interaction potentials that transfer poorly to molecular systems or conditions different than those used for model calibration. As a proof of concept, here, we employ , an automatic multiobjective optimization approach facilitating the development of lipid force fields, to refine specifically the bonded interaction parameters in building blocks of lipid models within the framework of the general Martini CG FF.

Transmembrane dimers of type 1 receptors sample alternate configurations: MD simulations using coarse grain Martini 3 versus AlphaFold2 Multimer.

Structures and dynamics of transmembrane (TM) receptor regions are key to understanding their signaling mechanism across membranes. Here we examine configurations of TM region dimers, assembled using the recent Martini 3 force field for coarse-grain (CG) molecular dynamics simulations. At first glance, our results show only a reasonable agreement with ab initio predictions using PREDDIMER and AlphaFold2 Multimer and with nuclear magnetic resonance (NMR)-derived structures.

An implementation of the Martini coarse-grained force field in OpenMM.

We describe a complete implementation of Martini 2 and Martini 3 in the OpenMM molecular dynamics software package. Martini is a widely used coarse-grained force field with applications in biomolecular simulation, materials, and broader areas of chemistry. It is implemented as a force field but makes extensive use of facilities unique to the GROMACS software, including virtual sites and bonded terms that are not commonly used in standard atomistic force fields.

Agent-Based Approach for (Peri-)Urban Inter-Modality Policies: Application to Real Data from the Lille Metropolis.

Transportation authorities have adopted more and more incentive measures (fare-free public transport, construction of park-and-ride facilities, etc.) to reduce the use of private cars by combining them with public transit. However, such measures remain difficult to assess with traditional transport models.

Facilitating CG Simulations with MAD: The MArtini Database Server.

The MArtini Database (MAD - https://mad.ibcp.fr) is a web server designed for the sharing of structures and topologies of molecules parametrized with the Martini coarse-grained (CG) force field.

Potential binding modes of the gut bacterial metabolite, 5-hydroxyindole, to the intestinal L-type calcium channels and its impact on the microbiota in rats.

Intestinal microbiota and microbiota-derived metabolites play a key role in regulating the host physiology. Recently, we have identified a gut-bacterial metabolite, namely 5-hydroxyindole, as a potent stimulant of intestinal motility via its modulation of L-type voltage-gated calcium channels located on the intestinal smooth muscle cells. Dysregulation of L-type voltage-gated calcium channels is associated with various gastrointestinal motility disorders, including constipation, making L-type voltage-gated calcium channels an important target for drug development.

Reported sleep duration reveals segmentation of the adult life-course into three phases.

Classically the human life-course is characterized by youth, middle age and old age. A wide range of biological, health and cognitive functions vary across this life-course. Here, using reported sleep duration from 730,187 participants across 63 countries, we find three distinct phases in the adult human life-course: early adulthood (19-33yrs), mid-adulthood (34-53yrs), and late adulthood (54+yrs).

Capturing the Recognition Dynamics of -Sulfonato-calix[4]arenes by Cytochrome c: Toward a Quantitative Free Energy Assessment.

Calix[]arenes' selective recognition of protein surfaces covers a broad range of timely applications, from controlling protein assembly and crystallization to trapping partially disordered proteins. Here, the interaction of -sulfonated calix-[4]-arenes with cytochrome c is investigated through all-atom, explicit water molecular dynamics simulations which allow characterization of two binding sites in quantitative agreement with experimental evidence. Free energy calculations based on the MM-PBSA and the attach-pull-release (APR) methods highlight key residues implicated in the recognition process and provide binding free energy results in quantitative agreement with isothermal titration calorimetry.

Dynamics of the secreted frizzled related protein Sizzled and potential implications for binding to bone morphogenetic protein-1 (BMP-1).

Sizzled (Szl) is both a secreted frizzled related protein (sFRP) and a naturally occurring inhibitor of the zinc metalloproteinase bone morphogenetic protein-1 (BMP-1), a key regulator of extracellular matrix assembly and growth factor activation. Here we present a new crystal structure for Szl which differs from that previously reported by a large scale (90°) hinge rotation between its cysteine-rich and netrin-like domains. We also present results of a molecular docking analysis showing interactions likely to be involved in the inhibition of BMP-1 activity by Szl.

Solid-State NMR Reveals Asymmetric ATP Hydrolysis in the Multidrug ABC Transporter BmrA.

The detailed mechanism of ATP hydrolysis in ATP-binding cassette (ABC) transporters is still not fully understood. Here, we employed P solid-state NMR to probe the conformational changes and dynamics during the catalytic cycle by locking the multidrug ABC transporter BmrA in prehydrolytic, transition, and posthydrolytic states, using a combination of mutants and ATP analogues. The P spectra reveal that ATP binds strongly in the prehydrolytic state to both ATP-binding sites as inferred from the analysis of the nonhydrolytic E504A mutant.

Functional Overexpression of Membrane Proteins in E. coli: The Good, the Bad, and the Ugly.

Overexpression of properly folded membrane proteins is a mandatory step for their functional and structural characterization. One of the most used expression systems for the production of proteins is Escherichia coli. Many advantageous strains combined with T7 expression systems have been developed over the years.

Oral-Hygiene-Related Mobile Apps in the French App Stores: Assessment of Functionality and Quality.

Mobile health apps can contribute to increased quality of individual oral hygiene behaviors. This study provides an overview and an evaluation of quality of oral-hygiene-related mobile apps currently available in Google Play Store and the French Apple App. A shortlist of nine apps was assessed by 10 oral health professionals using the Mobile App Rating Scale.