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DNA and lipid bilayers: self-assembly and insertion

DNA and lipid bilayers: self-assembly and insertion
DNA and lipid bilayers: self-assembly and insertion
DNA–lipid complexes are of biomedical importance as delivery vectors for gene therapy. To gain insight into the interactions of DNA with zwitterionic and cationic (dimyristoyltrimethylammonium propane (DMTAP)) lipids, we have used coarse-grained molecular dynamics simulations to study the self-assembly of DPPC and DPPC/DMTAP lipid bilayers in the presence of a DNA dodecamer. We observed the spontaneous formation of lipid bilayers from initial systems containing randomly placed lipids, water–counterions and DNA. In both the DPPC and DPPC/DMTAP simulations, the DNA molecule is located at the water–lipid headgroup interface, lying approximately parallel to the plane of the bilayer. We have also calculated the potential of mean force for transferring a DNA dodecamer through a DPPC/DMTAP bilayer. A high energetic barrier to DNA insertion into the hydrophobic core of the bilayer is observed. The DNA adopts a transmembrane orientation only in this region. Local bilayer deformation in the vicinity of the DNA molecule is observed, largely as a result of the DNA–DMTAP headgroup attraction.
molecular dynamics, coarse grain, dna, gene therapy
1742-5689
241-250
Khalid, Syma
90fbd954-7248-4f47-9525-4d6af9636394
Bond, Peter J.
08f46940-85e8-44c4-a368-d94342a10fd6
Holyoake, John
fa9e4627-3949-40c9-b3e6-4730e22b1ebc
Hawtin, Robert W.
b80d12ed-815b-40a8-ae01-f7e2557f4276
Sansom, Mark S.P.
ed30b4fc-bc73-4ad7-8c56-f51a67136e4e
Khalid, Syma
90fbd954-7248-4f47-9525-4d6af9636394
Bond, Peter J.
08f46940-85e8-44c4-a368-d94342a10fd6
Holyoake, John
fa9e4627-3949-40c9-b3e6-4730e22b1ebc
Hawtin, Robert W.
b80d12ed-815b-40a8-ae01-f7e2557f4276
Sansom, Mark S.P.
ed30b4fc-bc73-4ad7-8c56-f51a67136e4e

Khalid, Syma, Bond, Peter J., Holyoake, John, Hawtin, Robert W. and Sansom, Mark S.P. (2008) DNA and lipid bilayers: self-assembly and insertion. Journal of the Royal Society Interface, 5 (S3), supplement 3, 241-250. (doi:10.1098/rsif.2008.0239.focus). (PMID:18765335)

Record type: Article

Abstract

DNA–lipid complexes are of biomedical importance as delivery vectors for gene therapy. To gain insight into the interactions of DNA with zwitterionic and cationic (dimyristoyltrimethylammonium propane (DMTAP)) lipids, we have used coarse-grained molecular dynamics simulations to study the self-assembly of DPPC and DPPC/DMTAP lipid bilayers in the presence of a DNA dodecamer. We observed the spontaneous formation of lipid bilayers from initial systems containing randomly placed lipids, water–counterions and DNA. In both the DPPC and DPPC/DMTAP simulations, the DNA molecule is located at the water–lipid headgroup interface, lying approximately parallel to the plane of the bilayer. We have also calculated the potential of mean force for transferring a DNA dodecamer through a DPPC/DMTAP bilayer. A high energetic barrier to DNA insertion into the hydrophobic core of the bilayer is observed. The DNA adopts a transmembrane orientation only in this region. Local bilayer deformation in the vicinity of the DNA molecule is observed, largely as a result of the DNA–DMTAP headgroup attraction.

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Published date: 6 December 2008
Keywords: molecular dynamics, coarse grain, dna, gene therapy
Organisations: Chemistry, Computational Systems Chemistry

Identifiers

Local EPrints ID: 149547
URI: http://eprints.soton.ac.uk/id/eprint/149547
ISSN: 1742-5689
PURE UUID: 97ef6ff4-e1cf-4dff-92d4-7021f5ec07b1
ORCID for Syma Khalid: ORCID iD orcid.org/0000-0002-3694-5044

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Date deposited: 30 Apr 2010 13:16
Last modified: 14 Mar 2024 02:53

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Contributors

Author: Syma Khalid ORCID iD
Author: Peter J. Bond
Author: John Holyoake
Author: Robert W. Hawtin
Author: Mark S.P. Sansom

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