2 research outputs found
Gating-like Motions and Wall Porosity in a DNA Nanopore Scaffold Revealed by Molecular Simulations
Recently developed synthetic membrane pores composed of folded DNA enrich the current range of natural and engineered protein pores and of nonbiogenic channels. Here we report all-atom molecular dynamics simulations of a DNA nanotube (DNT) pore scaffold to gain fundamental insight into its atomic structure, dynamics, and interactions with ions and water. Our multiple simulations of models of DNTs that are composed of a six-duplex bundle lead to a coherent description. The central tube lumen adopts a cylindrical shape while the mouth regions at the two DNT openings undergo gating-like motions which provide a possible molecular explanation of a lower conductance state observed in our previous experimental study on a membrane-spanning version of the DNT (<i>ACS Nano</i> 2015, <i>9</i>, 1117ā26). Similarly, the central nanotube lumen is filled with water and ions characterized by bulk diffusion coefficients while the gating regions exhibit temporal fluctuations in their aqueous volume. We furthermore observe that the porous nature of the walls allows lateral leakage of ions and water. This study will benefit rational design of DNA nanopores of enhanced stability of relevance for sensing applications, of nanodevices with tunable gating properties that mimic gated ion channels, or of nanopores featuring defined permeation behavior
The Hidden Conformation of Lewis x, a Human Histo-Blood Group Antigen, Is a Determinant for Recognition by Pathogen Lectins
Histo-blood group epitopes are fucosylated
branched oligosaccharides
with well-defined conformations in solution that are recognized by
receptors, such as lectins from pathogens. We report here the results
of a series of experimental and computational endeavors revealing
the unusual distortion of histo-blood group antigens by bacterial
and fungal lectins. The Lewis x trisaccharide adopts a rigid closed
conformation in solution, while crystallography and molecular dynamics
reveal several higher energy open conformations when bound to the <i>Ralstonia solanacearum</i> lectin, which is in agreement with
thermodynamic and kinetic measurements. Extensive molecular dynamics
simulations confirm rare transient Le<sup>x</sup> openings in solution,
frequently assisted by distortion of the central N-acetyl-glucosamine
ring. Additional directed molecular dynamic trajectories revealed
the role of a conserved tryptophan residue in guiding the fucose into
the binding site. Our findings show that conformational adaptation
of oligosaccharides is of paramount importance in cell recognition
and should be considered when designing anti-infective glyco-compounds