Marzinek JK
The antibiotic darobactin mimics a β-strand to inhibit outer membrane insertase
Antibiotics that target Gram-negative bacteria in new ways are needed to resolve the antimicrobial resistance crisis1,2,3. Gram-negative bacteria are protected by an additional outer membrane, rendering proteins on the cell surface attractive drug targets4,5.
ReadAntibody affinity versus dengue morphology influences neutralization
Different strains within a dengue serotype (DENV1-4) can have smooth, or “bumpy” surface morphologies with different antigenic characteristics at average body temperature (37°C). We determined the neutralizing properties of a serotype cross-reactive human monoclonal antibody (HMAb) 1C19 for strains with differing morphologies within the DENV1 and DENV2 serotypes.
ReadCharacterizing the Hydration Properties of Proton Binding Sites in the ATP Synthase c-Rings of Bacillus Species.
The membrane-embedded domain of ATP synthases contains the c-ring, which translocates ions across the membrane, and its resultant rotation is coupled to ATP synthesis in the extramembranous domain. During rotation, the c-ring becomes accessible on both sides of the lipid bilayer to solvent via channels connected to the other membrane-embedded component, the a subunit, and thereby allows the ion to be released into the solvent environment.
ReadMolecular dynamics simulations of bacterial outer membrane lipid extraction: Adequate sampling?
The outer membrane of Gram-negative bacteria is almost exclusively composed of lipopolysaccharide in its outer leaflet, whereas the inner leaflet contains a mixture of phospholipids. Lipopolysaccharide diffuses at least an order of magnitude slower than phospholipids, which can cause issues for molecular dynamics simulations in terms of adequate sampling.
ReadComputational modelling of flavivirus dynamics: The ins and outs
- Computational methods integrating experimental data help elucidate viral life cycle. - Viruses are dynamic and have complex interactions with a variety of host factors. - We can now model the complex interplay of proteomic and genomic components. - Molecular biology, genomics, and computation complement structural methods.
ReadComputational modelling of flavivirus dynamics: The ins and outs
Enveloped viruses such as the flaviviruses represent a significant burden to human health around the world, with hundreds of millions of people each year affected by dengue alone. In an effort to improve our understanding of the molecular basis for the infective mechanisms of these viruses, extensive computational modelling approaches have been applied to elucidate their conformational dynamics.
ReadExtending the Martini coarse-grained forcefield to N-glycans
Glycans play a vital role in a large number of cellular processes. Their complex and flexible nature hampers structure-function studies using experimental techniques. Molecular dynamics (MD) simulations can help in understanding dynamic aspects of glycans if the forcefield (FF) parameters used can reproduce key experimentally observed properties.
ReadA benzene-mapping approach for uncovering cryptic pockets in membrane-bound proteins
Molecular dynamics (MD) simulations in combination with small organic probes present in the solvent have previously been used as a method to reveal cryptic pockets that may not have been identified in experimental structures. We report such a method implemented within the CHARMM forcefield to effectively explore cryptic pockets on the surfaces of membrane-embedded proteins using benzene as a probe molecule.
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