Martini Coarse-Grained Force Field: Extension to DNA

López, César A.; Rzepiela, Andrzej J.; Vries, de Alex; Dijkhuizen, Lubbert; Huenenberger, Philippe H.; Marrink, Siewert J.

doi:10.1021/acs.jctc.5b00286

Cited by 273 publications

(328 citation statements)

References 76 publications

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“…40,41 In agreement with experimental results, a DEB was stable over a 5 microsecond duration with the 4 nm thick DMPC bilayer encircled by the 2 nm thick dsDNA rim. The interaction of the alkyl chains (Figure 4a-b, red) with the lipid bilayer could also be clearly observed.…”

Section: -11supporting

confidence: 87%

DNA-Encircled Lipid Bilayers

Iric

Subramanian²,

Oertel

et al. 2018

Preprint

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Lipid bilayers and lipid-associated proteins play a crucial role in biology. As in vivo studies and manipulation are inherently difficult, several membrane-mimetic systems have been developed to enable investigation of lipidic phases, lipid-protein interactions, membrane protein function and membrane structure in vitro. Controlling the size and shape, or site-specific functionalization is, however, difficult to achieve with established membrane mimetics based on membrane scaffolding proteins, polymers or peptides. In this work, we describe a route to leverage the unique programmability of DNA nanotechnology and create DNA-encircled bilayers (DEBs), which are made of multiple copies of an alkylated oligonucleotide hybridized to a single-stranded minicircle. To stabilize the hydrophobic rim of the lipid bilayer, and to prevent formation of lipid vesicles, we introduced up to 2 alkyl chains per helical that point to the inside of the toroidal DNA ring and interact with the hydrophobic side chains of the encapsulated lipid bilayer. The DEB approach described herein provides unprecedented control of size, and allows the orthogonal functionalizations and arrangement of engineered membrane nanoparticles and will become a valuable tool for biophysical investigation of lipid phases and lipid-associated proteins and complexes including structure determination of membrane proteins and pharmacological screenings of membrane proteins.

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Section: -11supporting

confidence: 87%

DNA-Encircled Lipid Bilayers

Iric

Subramanian²,

Oertel

et al. 2018

Preprint

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“…In view of the recent publication of a DNA model within the framework of this force field 29 and given the structural similarities between siRNA and a short DNA fragment in terms of their negatively charged anionic phosphodiester backbones, we represent siRNA by this model using double-stranded DNA in the canonical A form. In the DNA force field, the double-helical structure is imposed via an elastic network.…”

Section: Coarse-grained Molecular Dynamics Simulations Based On Mamentioning

confidence: 99%

“…28 It is particularly interesting to examine its capabilities, since only very recently a DNA model was released employing this force field. 29 We investigate the extension of this model to siRNA, focusing on the representation with polarizable water 30 and full long-range electrostatic interactions, as those are crucial in the complexation of siRNA with PEI copolymers. For the latter, we choose polyethylene glycol (PEG)-grafted linear PEI, following our earlier work on DNA nanoparticle shape control.…”

Section: Introductionmentioning

confidence: 99%

Systematic coarse-grained modeling of complexation between small interfering RNA and polycations

Wei

Luijten

2015

The Journal of Chemical Physics

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All-atom molecular dynamics simulations can provide insight into the properties of polymeric gene-delivery carriers by elucidating their interactions and detailed binding patterns with nucleic acids. However, to explore nanoparticle formation through complexation of these polymers and nucleic acids and study their behavior at experimentally relevant time and length scales, a reliable coarse-grained model is needed. Here, we systematically develop such a model for the complexation of small interfering RNA (siRNA) and grafted polyethyleneimine copolymers, a promising candidate for siRNA delivery. We compare the predictions of this model with all-atom simulations and demonstrate that it is capable of reproducing detailed binding patterns, charge characteristics, and water release kinetics. Since the coarse-grained model accelerates the simulations by one to two orders of magnitude, it will make it possible to quantitatively investigate nanoparticle formation involving multiple siRNA molecules and cationic copolymers. C 2015 AIP Publishing LLC. [http://dx

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“…The interactions between CG beads can be obtained either with a top-down approach, i.e., fitted to reproduce key experimental data, especially thermodynamic properties, or with the bottom-up approach, employing methods such as inverse Monte Carlo [95], iterative Boltzmann inversion (IBI) [96], force matching [97][98][99], and relative entropy [100][101][102]. Recently, also the popular MARTINI force field [103] was extended to DNA [104]. On an even coarser level, the DNA can be modeled as a cylinder with charge located on the sites corresponding to the phosphate group in the B-form of DNA [41,42,105].…”

Section: Model Interaction Potential Parametrization In Dna Arraysmentioning

confidence: 99%

Molecular Dynamics Simulation of High Density DNA Arrays

2018

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Densely packed DNA arrays exhibit hexagonal and orthorhombic local packings, as well as a weakly first order transition between them. While we have some understanding of the interactions between DNA molecules in aqueous ionic solutions, the structural details of its ordered phases and the mechanism governing the respective phase transitions between them remains less well understood. Since at high DNA densities, i.e., small interaxial spacings, one can neither neglect the atomic details of the interacting macromolecular surfaces nor the atomic details of the intervening ionic solution, the atomistic resolution is a sine qua non to properly describe and analyze the interactions between DNA molecules. In fact, in order to properly understand the details of the observed osmotic equation of state, one needs to implement multiple levels of organization, spanning the range from the molecular order of DNA itself, the possible ordering of counterions, and then all the way to the induced molecular ordering of the aqueous solvent, all coupled together by electrostatic, steric, thermal and direct hydrogen-bonding interactions. Multiscale simulations therefore appear as singularly suited to connect the microscopic details of this system with its macroscopic thermodynamic behavior. We review the details of the simulation of dense atomistically resolved DNA arrays with different packing symmetries and the ensuing osmotic equation of state obtained by enclosing a DNA array in a monovalent salt and multivalent (spermidine) counterions within a solvent permeable membrane, mimicking the behavior of DNA arrays subjected to external osmotic stress. By varying the DNA density, the local packing symmetry, and the counterion type, we are able to analyze the osmotic equation of state together with the full structural characterization of the DNA subphase, the counterion distribution and the solvent structural order in terms of its different order parameters and consequently identify the most important contribution to the DNA-DNA interactions at high DNA densities.

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Martini Coarse-Grained Force Field: Extension to DNA

Cited by 273 publications

References 76 publications

DNA-Encircled Lipid Bilayers

DNA-Encircled Lipid Bilayers

Systematic coarse-grained modeling of complexation between small interfering RNA and polycations

Molecular Dynamics Simulation of High Density DNA Arrays

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