MP
Molecular basis for multidrug efflux by an anaerobic-associated RND transporter.
Lawrence R, Athar M, Uddin MR, Adams C, Sousa JS, Durrant O, Lellman S, Sutton L, Keevil CW, Patel N, Prosser CE, McMillan D, Zgurskaya HI, Vargiu AV, Ahdash Z, Reading E.
Nat Commun. 2025 Dec 3;16(1):10601.
doi: 10.1038/s41467-025-65565-7.
PMID: 41339309.
Cryo-EM structure of an anaerobic-associated RND transporter => unique architecture in its substrate-binding pocket that accommodates diverse antibiotics and toxins.
Conformational flexibility within the transporter’s periplasmic domain enables promiscuous substrate recognition, while proton-coupled transport drives efflux against concentration gradients.
Structure-Based Drug Design Targeting the Substrate-Binding Pocket of MexB.
Nanjan P.
Protein J. 2026 Feb 18.
doi: 10.1007/s10930-026-10321-z. Online ahead of print.
PMID: 41708976.
SBDD to identify compounds that specifically bind to the substrate-binding pocket of MexB, blocking efflux activity.
MD, virtual screening, and functional assays => binding modes and inhibitory effects of lead compounds, revealing critical interactions that stabilize the inhibitor-bound state.
In silico Screening of Plant Compounds to Inhibit MexB Efflux Protein for the Enhancement of Meropenem Resistance against Pseudomonas aeruginosa MDR Infections.
Nanjan P, Bose BV.
Recent Adv Antiinfect Drug Discov. 2025;20(3):223-250.
doi: 10.2174/0127724344343717250404114236.
PMID: 41315177.
in silico screening of plant-derived compounds to identify potential MexB inhibitors that could restore meropenem susceptibility.
Molecular docking, virtual screening, and MD => compounds that bind to MexB’s substrate-binding pocket, blocking efflux activity.
Stereochemical insight for MexXY-OprM efflux system inhibition in Pseudomonas aeruginosa from a pool of dihydro and tetrahydro berberine derivatives.
Tosiani VD, Di Gregorio A, Giorgini G, Vignaroli C, Mari G, Mantellini F, Favi G, Minnelli C, Mobbili G, Simoni S, Galeazzi R.
Chem Biol Interact. 2026 Jan 25;424:111850.
doi: 10.1016/j.cbi.2025.111850. Epub 2025 Nov 28.
PMID: 41319800.
Study of the inhibitory potential of dihydro and tetrahydro berberine derivatives, revealing how their stereochemistry influences binding to MexXY-OprM and efflux inhibition.
MD, SD mutagenesis, and functional assays => specific berberine derivatives that effectively block substrate transport, restoring antibiotic susceptibility.
Structural basis of specific lysine transport by Pseudomonas aeruginosa permease LysP.
Bicer D, Matsuoka R, Moumbock AFA, Sukumar P, Suades A, Cheruvara H, Quigley A, Drew D, Pardon E, Steyaert J, Henderson PJF, Caffrey M, Griese JJ, Nji E.
Nat Commun. 2025 Dec 4.
doi: 10.1038/s41467-025-66618-7. Online ahead of print.
PMID: 41345107.
Lysine transport in P. aeruginosa is mediated by LysP (critical role in bacterial metabolism and virulence).
Here : cryo-EM structure of LysP => substrate-binding site tailored for high-affinity lysine recognition through a network of hydrogen bonds and electrostatic interactions.
Description of the conformational changes that facilitate lysine translocation across the membrane, coupling transport to pmf.
Structural basis of sodium ion-dependent carnitine transport by OCTN2.
Davies JS, Zeng YC, Briot C, Brown SHJ, Ryan RM, Stewart AG.
Nat Commun. 2025 Nov 29.
doi: 10.1038/s41467-025-66867-6. Online ahead of print.
PMID: 41318751.
OCTN2 = crucial role in cellular energy metabolism by mediating sodium-dependent carnitine uptake.
Here : cryo-EM structure of OCTN2 => sodium binding induces conformational changes that facilitate carnitine transport.
Key residues involved in the substrate-binding site + transport mechanism (alternating access) are proposed.
TMEM170 proteins are lipid scramblases associated with bridge-type lipid transporters BLTP1/Csf1.
Rocha-Roa C, Chandran Blair P, Sidhu G, Álvarez D, Davey M, Conibear E, Vanni S.
Nat Struct Mol Biol. 2026 Feb;33(2):215-219.
doi: 10.1038/s41594-025-01716-0. Epub 2025 Nov 26.
PMID: 41299140.
TMEM170 = newly identified lipid scramblases that facilitate the bidirectional movement of PLs across cellular membranes (essential for membrane homeostasis and signaling).
cryo-EM and functional assays => association of TMEM170 with bridge-type lipid transporters BLTP1/Csf1, forming a complex that coordinates lipid transfer and membrane remodeling. TMEM170’s scramblase activity is coupled to the lipid transport function of BLTP1/Csf1 : cooperative role in lipid dynamics.
De novo design of GPCR exoframe modulators.
Cheng S, Guo J, Zhou YL, Luo X, Zhang G, Zhang YZ, Yang Y, Xie J, Xu P, Shen DD, Zang S, Yang H, Zhen X, Zhang M, Zhang Y.
Nature. 2026 Feb 16.
doi: 10.1038/s41586-025-09957-1. Online ahead of print.
PMID: 41699180.
de novo design approach to create “exoframe modulators,” small molecules that bind to extracellular allosteric sites on GPCRs and stabilize specific conformations.
Computational modeling, structural biology, and functional assays to validate the modulators’ ability to fine-tune receptor activity => novel strategy for GPCR-targeted drug discovery.
Structural basis for selective inhibition of human GABA transporter GAT3.
Mortensen JS, Bavo F, Jensen MH, Pedersen APS, Storm JP, Pape T, Frølund B, Wellendorph P, Shahsavar A.
Nat Commun. 2026 Jan 29;17(1):1774.
doi: 10.1038/s41467-026-68479-0.
PMID: 41611703.
human GABA transporter GAT3 regulates inhibitory neurotransmission by clearing GABA from the synaptic cleft (=> target for treating neurological disorders).
Here :cryo-EM structure of GAT3 in complex with a selective inhibitor.
Key interactions within the binding pocket that differentiate GAT3 from other GABA transporters, providing a template for designing selective inhibitors.
ProtRAP-LM: Efficient Protein Relative Accessibility Prediction and Proteome-wide Membrane Protein Screening.
Wang L, Kang K, Song C.
Genomics Proteomics Bioinformatics. 2026 Feb 15:qzag013.
doi: 10.1093/gpbjnl/qzag013. Online ahead of print.
PMID: 41692997.
Predicting the relative accessibility of MPs is crucial for understanding their functional states and interactions.
Here : ProtRAP-LM, ML-based tool that predicts protein accessibility by integrating structural, evolutionary, and biophysical features.
Application in proteome-wide screening, identifying MPs with exposed functional sites and potential drug-binding pockets.
In situ structural studies of membrane protein megacomplexes.
Sun S, Sui SF.
Curr Opin Struct Biol. 2026 Feb 12;97:103222.
doi: 10.1016/j.sbi.2026.103222. Online ahead of print.
PMID: 41687505.
Review on recent advances in cryo-electron tomography and subtomogram averaging => high-resolution megacomplexes (respiratory supercomplexes and efflux pumps directly in intact cells or membranes).
Why transport matters: an update on carrier proteins in Apicomplexan parasites.
Haase S, Sateriale A.
Curr Opin Microbiol. 2025 Dec;88:102663.
doi: 10.1016/j.mib.2025.102663. Epub 2025 Sep 8.
PMID: 40925062.
Carrier proteins in Apicomplexan parasites = essential for nutrient acquisition, ion homeostasis, and drug resistance.
Here : review on recent advances in understanding the structure, function, and regulation of these transporters, highlighting their roles in parasite survival and pathogenesis.
Single-molecule dynamics reveal ATP binding alone powers substrate translocation by an ABC transporter.
Christoph Nocker, Matija Pečak, Tobias Nocker, Amin Fahim, Lukas Sušac, Robert Tampé
bioRxiv 2025.11.27.690960;
doi: https://doi.org/10.1101/2025.11.27.690960.
ABC transporters utilize ATP hydrolysis to drive substrate translocation across membranes, but the precise energetic coupling between ATP binding and transport remains debated.
Here : single-molecule dynamics to demonstrate that ATP binding alone, without hydrolysis, is sufficient to power substrate translocation in an ABC transporter.
Membranes
When membrane proteins prefer lipids.
Lyman E.
Nat Chem Biol. 2025 Nov 28.
doi: 10.1038/s41589-025-02084-y. Epub ahead of print.
PMID: 41315780.
A news and Views on ”Molecular basis for the regulation of membrane proteins through preferential lipid solvation by Nathan Bernhardt et al.”, already adverized in 20251029_membranes and molecules digest.
Structural basis of caveolin-driven membrane bending.
Connelly SM, Bergner L, Tiwari A, Brant TS, Medford S, Ramesh S, Tidwell ED, Yoo Y, Xiao K, Gentry J, Chang L, Han B, Rangamani P, Doktorova M, Kenworthy AK, Mosalaganti S, Ohi MD.
bioRxiv [Preprint]. 2026 Feb 17:2026.02.05.703862.
doi: 10.64898/2026.02.05.703862.
PMID: 41717096.
Cryo-EM, MD and biophysical assays => how caveolin proteins drive membrane curvature.
Caveolin oligomers insert wedge-like helices into the lipid bilayer, locally deforming the membrane and recruiting specific lipids to stabilize the curved structure.
Structural and dynamics of apoA-1 mimetic peptide lipid nanodisc assemblies: A molecular dynamics study.
Ravi R, Salnikov ES, Bechinger B, Tarek M.
Biochim Biophys Acta Biomembr. 2025 Nov 29:184495.
doi: 10.1016/j.bbamem.2025.184495. Online ahead of print.
PMID: 41325958.
ApoA-1 mimetic peptides = widely used to form lipid NDs.
Here : MD to investigate the structural dynamics and stability of apoA-1 peptide-lipid ND assemblies, revealing how peptide-lipid interactions govern nanodisc formation and properties.
The conformational flexibility of apoA-1 peptides and the lipid composition of the nanodiscs influence their size, shape, and stability.
Molecular Interactions of Fluoroquinolone Antibiotics with Lipid Membranes.
Ralph D, Goode A, Yeh V, Blair JMA, Williams P, Bonev BB.
Langmuir. 2026 Feb 17;42(6):4386-4396.
doi: 10.1021/acs.langmuir.5c04836. Epub 2025 Dec 2.
PMID: 41329960.
Fluoroquinolones interact with lipid membranes, influencing their distribution, accumulation, and antimicrobial activity.
Here : molecular interactions of fluoroquinolones with model lipid membranes, using a combination of biophysical techniques and MD simulations.
Fluoroquinolones partition into lipid bilayers, affecting membrane fluidity and permeability, which in turn impacts their antibacterial efficacy.
Quantifying interleaflet coupling of phase behavior and observing anti-registered phases in asymmetric lipid bilayers.
Kristen B. Kennison-Cook, Averi M. Cooper, Frederick A. Heberle
bioRxiv 2026.02.17.706271.
doi: https://doi.org/10.64898/2026.02.17.706271
Model asymmetric lipid bilayers = powerful platform for probing how lateral phase behavior in one leaflet is coupled to that of the opposing leaflet.
Here : calcium-induced hemifusion to generate asymmetric GUV (aGUVs) and investigate how lipid composition modulates interleaflet coupling of liquid-liquid phase separation.
=> modest changes in lipid chain length can markedly alter asymmetric miscibility boundaries.
Accurate Single-Particle Tracking and Diffusion Measurement in Freestanding Lipid Bilayers and Model Membranes.
Van Ye LA, Michael RD, Meyer JJ, Peña SM, Bailey DJ, Keranen-Burden LM, Burden DL.
Anal Chem. 2025 Dec 8.
doi: 10.1021/acs.analchem.5c05037. Online ahead of print.
PMID: 41359355.
Single-particle tracking = powerful tool for studying the dynamics of molecules within lipid bilayers, but achieving accurate measurements in freestanding membranes remains challenging.
Here : optimized method for high-precision single-particle tracking and diffusion measurement in model membranes, combining advanced microscopy with computational analysis.
=> can resolve heterogeneous diffusion behaviors, revealing insights into lipid-molecule interactions and membrane organization.
Molecules
Vinyl ether maleic acid block copolymers: a versatile platform for tunable self-assembled lipid nanodiscs and membrane protein characterization.
Shah MZ, Okorafor E, Rotich NC, Henoch Q, Thapa Acharya R, Page RC, Lorigan GA, Konkolewicz D.
Polym Chem. 2025 Dec 1.
doi: 10.1039/d5py00767d. Online ahead of print.
PMID: 41357811.
Vinyl ether maleic acid block copolymers = versatile platform for creating self-assembled lipid NDs.
Here : how the tunable properties of these copolymers enable the formation of NDs with controlled size, stability, and lipid composition. Compatibility with structural and functional assays.
Methods
Expanding enzyme functionality through site-specific incorporation of noncanonical amino acids.
Shaik SP, Li A, Guo J, Niu W.
Trends Biochem Sci. 2026 Feb 9:S0968-0004(25)00300-7.
doi: 10.1016/j.tibs.2025.12.008. Online ahead of print.
PMID: 41667292.
Review on recent advances in site-specific noncanonical amino acids (ncAAs) incorporation using orthogonal translation systems, focusing on applications in enzyme engineering and synthetic biology.
ncAAs can enhance enzyme activity, substrate specificity, and are resistant to harsh conditions.
Cell-free systems for expression of transmembrane protein.
Farooq K, Hamdani SDA, Babar MM, Rajadas J.
Prog Mol Biol Transl Sci. 2026;219:1-19.
doi: 10.1016/bs.pmbts.2025.09.001. Epub 2025 Sep 19.
PMID: 41688133.
Microbio
Targeting bacterial kinases as a strategy to counteract antibiotic resistance.
Buffa V, Kowalewski J, Qi G, Deutscher R, Cica M, Richardoz M, Tomaszczyk M, Krämer A, Knapp S, Dunyach-Remy C, Rox K, Guichou JF, Lionne C, Hausch F.
Commun Chem. 2025 Dec 4;8(1):390.
doi: 10.1038/s42004-025-01794-7.
PMID: 41345223.
Bacterial kinases = promising targets for combating atbR, as they regulate critical pathways involved in cell wall synthesis, metabolism, and virulence.
Antagonistic drug interactions protect commensal Bacteroidaceae from macrolides via an RND-type efflux pump.
Müller P, Schmidtchen V, de la Cuesta-Zuluaga J, Pérez Jiménez L, Gekeler C, Mateus A, Maier L.
Gut Microbes. 2025 Dec 31;17(1):2596806.
doi: 10.1080/19490976.2025.2596806. Epub 2025 Dec 9.
PMID: 41362921.
An RND-type efflux pump in Bacteroidaceae confers macrolide resistance by expelling antibiotics from the cell, and that this resistance is further enhanced by antagonistic drug interactions within the microbiome.
Genetic, biochemical, and metagenomic analyses to elucidate how these interactions protect commensal bacteria from antibiotic stress.
Miscellaneous
Going for gold: engineering success in elite winter sports.
Commun Eng. 2026 Feb 16;5(1):31.
doi: 10.1038/s44172-026-00609-4.
PMID: 41699117.
Engineering and technology are playing an increasingly pivotal role in optimizing performance in elite winter sports, from equipment design to athlete training.
Here : how advancements in materials science, biomechanics, and data analytics are being integrated to enhance speed, precision, and safety in sports like skiing, bobsleigh, and ice hockey.
Will self-driving ‘robot labs’ replace biologists? Paper sparks debate.
Callaway E.
Nature. 2026 Feb 18.
doi: 10.1038/d41586-026-00453-8. Epub ahead of print.
PMID: 41708825.
A recent paper proposing the use of autonomous “robot labs” for HT biological research has ignited a debate about the future role of human biologists.
AI-driven systems can perform experiments, analyze data, and even design follow-up studies with minimal human intervention, potentially accelerating discovery and reducing costs. Critics argue that while robot labs may increase efficiency, they risk overshadowing the creativity, intuition, and ethical judgment that human researchers bring to science.
=> need to balance automation with human expertise to ensure responsible and innovative progress in biology.
Microsoft team creates ‘revolutionary’ data-storage system that lasts for millennia.
Gibney E.
Nature. 2026 Feb 18.
doi: 10.1038/d41586-026-00502-2. Epub ahead of print.
PMID: 41708826.
Microsoft researchers have developed a data-storage system called “Project Silica” => ultrafast laser optics to encode data in quartz glass, promising durability for thousands of years.
This technology addresses the growing challenge of digital data preservation by resisting environmental degradation, unlike traditional magnetic or optical storage.
Fentanyl vaccine enters clinical trials
Emily Mullin WIRED (Science) Dec 3, 2025
A vaccine that keeps the opioid drug fentanyl out of the brain is about to start clinical trials in the Netherlands. The shot works by pairing a fentanyl-like molecule with a carrier protein, which is chunky enough to trigger the immune system to make antibodies, even though fentanyl isn’t big enough to do that on its own. Once primed, the immune system should attack any future fentanyl that enters the blood, preventing the ‘high’ and the possibility of overdose, a big benefit in places such as the United States, where more than half a million people have died from opioid overdoses since 2012. The vaccine could be suitable for people in addiction recovery programs or people who might be accidentally exposed to fentanyl mixed in with other drugs.