Stability and dynamics of membrane-spanning DNA nanopores.
Recently developed DNA-based analogues of membrane proteins have advanced synthetic biology. A fundamental question is how hydrophilic nanostructures reside in the hydrophobic environment of the membrane. Here, we use multiscale molecular dynamics (MD) simulations to explore the structure, stability and dynamics of an archetypical DNA nanotube inserted via a ring of membrane anchors into a phospholipid bilayer. Coarse-grained MD reveals that the lipids reorganize locally to interact closely with the membrane-spanning section of the DNA tube. Steered simulations along the bilayer normal establish the metastable nature of the inserted pore, yielding a force profile with barriers for membrane exit due to the membrane anchors. Atomistic, equilibrium simulations at two salt concentrations confirm the close packing of lipid around of the stably inserted DNA pore and its cation selectivity, while revealing localized structural fluctuations. The wide-ranging and detailed insight informs the design of next-generation DNA pores for synthetic biology or biomedicine.
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
Vishal
V
Maingi
Department of Chemistry, Institute of Structural Molecular Biology, University College London, London WC1H 0AJ, UK.
Jonathan R
JR
Burns
Groningen Biomolecular Sciences and Biotechnology Institute and Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands.
Jaakko J
JJ
Uusitalo
Department of Chemistry, Institute of Structural Molecular Biology, University College London, London WC1H 0AJ, UK.
Stefan
S
Howorka
Groningen Biomolecular Sciences and Biotechnology Institute and Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands.
Siewert J
SJ
Marrink
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
Mark S P
MS
Sansom
D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D058608:Nanopores; D049329:Nanostructures / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism
D008051:Lipid Bilayers; D008563:Membrane Lipids; D008565:Membrane Proteins; D010743:Phospholipids; D004247:DNA