Atomistic Simulations and Design in Biology
Elucidating the effect of poly(ethylene terephthalate) chain structure on its enzymatic degradation behaviour
Polyethylene terephthalate, chemical modification, crystallinity, structural characterization, thermal properties, enzymatic degradation
ReadStitched peptides as potential cell permeable inhibitors of oncogenic DAXX protein
DAXX (Death Domain Associated Protein 6), initially identified as a potentiator of apoptosis, is known to play crucial roles in several vital biological pathways, including chromatin remodeling, transcription regulation, DNA repair, and innate immunity. Its increased expression has been observed in diverse, epidemiologically prevalent cancers
ReadElucidating the effect of poly(ethylene terephthalate) chain structure on its enzymatic degradation behaviour
Polyethylene terephthalate (PET) is a widely used thermoplastic polymer, but its excessive use and poor waste management pose environmental challenges.
ReadA high-throughput microfluidic mechanoporation platform to enable intracellular delivery of cyclic peptides in cell-based assays
Cyclic peptides are poised to target historically difficult to drug intracellular protein–protein interactions, however, their general cell impermeability poses a challenge for characterizing function.
ReadNature-inspired synthetic oligourea foldamer channels allow water transport with high salt rejection
Biomimetic membranes incorporating artificial water channels (AWCs) are being developed for industrial water purification. Designing AWCs to achieve high water permeation with salt rejection is a challenge. We designed and synthesized oligourea foldamers, which form predictable helical structures that can be used to create biomimetic porin-like architectures. Two of these foldamers (H2OC1 and H2OC2) allow superior water permeability and almost total salt rejection across lipid membranes. Solid-state NMR, cryo-EM, and molecular dynamics analyses suggest proper insertion of foldamers into lipid vesicles. The H2OC1 crystal structure shows hydrophilic pores of diameters 4.8 and 6.4 Å. The oligourea helices pack together by hydrophobic and salt bridge interactions to build two channel-like assemblies. Besides their proteolytic stability and microbial resistance, the sequence of foldamers can be tailored to regulate selectivity. The ease of designing, synthesizing, and purifying oligourea foldamers is an added advantage. Our findings can help to develop novel AWCs for water purification applications.
ReadObservation of multiple protein temperature transitions dependent upon the chemical environment
Surgical site infections (SSI) are a clinical and economic burden. Suture-associated SSI may develop when bacteria colonize the suture surface and form biofilms that are resistant to antibiotics.
ReadDesigner co-beta-peptide copolymer selectively targets resistant and biofilm Gram-negative bacteria. Biomaterials
New antimicrobials are urgently needed to combat Gram-negative bacteria, particularly multi-drug resistant (MDR) and phenotypically resistant biofilm species. At present, only sequence-defined alpha-peptides (e.g. polymyxin B) can selectively target Gram-negative bacterial lipopolysaccharides. We show that a copolymer, without a defined sequence, shows good potency against MDR Gram-negative bacteria including its biofilm form.
ReadEngineering an Autonomous VH Domain to modulate intracellular pathways and to Interrogate the eIF4F Complex
Approaches have been devised to increase the discovery rate of intrabodies but often these yield results that aren’t functional in cells. Here the authors engineer and optimise an autonomous and disulphide-free human VH domain for intracellular expression, and they identify several VH domain binders against eIF4E.
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