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. Dna nanotechnology and its biological applications1 chapter of book. Allatom and coarsegrained md simulations are now relatively. They are usually dedicated to computational modeling of specific molecules.
In silico modelling of dna nanostructures sciencedirect. Stimulated by the dirth of reliable coarsegrained singlestranded dna models, a the aksimentiev and ha groups collaborated to create the first computational model of dna specifically optimized for singlestranded dna using. Nanotechnology is often defined as the study of materials and devices with features on a scale below 100 nanometers. Simulations of computational models of dna have the potential to offer insight into the operation of. The representation of the dna is \cpk for the coarsegrained models, and \vdw for the atomic model. We illustrate some of the range of dna nanotechnology systems to which the model is being applied, as well as the insights it can provide into fundamental biophysical properties of dna. As an example, we use a cadnano design of a sixhelix cylinder structure, which is provided in the tutorial archive. We first used dna average structures extracted from a 15 ns molecular dynamics md simulation of 2bop. More than 20 coarsegrained cg dna models have been developed for simulating the behavior of this molecule under various conditions, including those requ. Dna mutation simulation this work is licensed under a creative commons attributionnoncommercialsharealike 4. Multiresolution simulation of a curved sixhelix bundle of dna. B cryoelectron microscopy reconstruction of the dna pointer structure. Coarsegrained models are widely used for molecular modeling of biomolecules at various granularity levels a wide range of coarsegrained models have been proposed.
Mar 25, 2021 the methods we use or develop are largely based on statistical mechanics, molecular modeling and simulations, stochastic dynamics, coarsegraining, bioinformatics, machine learning, and polymercolloidal physics. Dec 18, 2017 we also examined the performance of the model for multilayer systems by simulation of dna origami with published cryoelectron microscopy and atomic force microscopy structures. Coarsegraining dna for simulations of dna nanotechnology core. Overstretching at 23 c occurs at 74 pn in the model, about 67 pn higher than the experimental value at equivalent salt conditions. Such a model helps us to reduce the computational costs to simulate long dna plasmids while keeping many details to obtain more information about the conformations of the supercoils. Louis,b flavio romano,a petr sulc,b chris tian matek, benedict e. To simulate long time and length scale processes involving dna it is necessary to use a coarsegrained description. However, none of these models reproduces the dna polymorphism associated with conformational changes in the ribose rings of the dna backbone. Development of coarsegraining dna models for single.
Differentiating parallel and antiparallel dna duplexes in. Optimizing dna nanotechnology through coarsegrained modeling. Molecular dynamics simulation of supercoiled dna rings. The general design principles from dna nanotechnology can be applied to rna, but because specific.
Coarse grained models are widely used for molecular modeling of biomolecules at various granularity levels. For more complex systems, however, rational design and optimization can become difficult. The mechanism of overstretching is always forceinduced melting by. These changes make an essential contribution to the dna local. On the biophysics and kinetics of toeholdmediated dna strand displacement, nucl. A practical guide to dna origami simulations using namd. Pdf dynamic dna nanotechnology involves the creation of nanoscale devices made of dna. Optimizing dna nanotechnology through coarse grained modeling. We discuss here the theoretical underpinnings and history of coarsegraining and summarize the state of the field. Notably, the aksimentiev group have simulated a number of origami nanostructures 30,3234, including even an origami nanopore. Then, another viral enzyme called integrasehides the proviraldna into the cells dna.
Maxim paliy 1,2, roderick melnik 1,3 and bruce a shapiro 4. Computational studies of dna separations in microfabricated. Coarsegraining dna for simulations of dna nanotechnology, phys. Note here that the wlc model for spring forces is the most commonly used model in dynamic dna simulations 17, 18. Oxdna, our recentlydeveloped coarsegrained dna model, is. The force exerted by electrical field can be expressed by. Multiresolution simulations of selfassembled dna nanostructures.
Physical chemistry chemical physics 15 47, 2039520414, 20. More than 20 coarsegrained cg dna models have been developed for simulating the behavior of this molecule under various conditions, including those required for nanotechnology. Coarsegraining cg is a common approach to handle large dna systems that cannot be dealt with by means of atomistic models. Overstretching at 23 c occurs at 74 pn in the model, about 67 pn higher than the experimental value. To address this challenge, multiscale approaches, including coarsegraining methods, become necessary. Researchers in the field have created static structures such as two and threedimensional crystal lattices, nanotubes.
Brownian dynamics simulations of dna complexation with. Voth, editor, coarsegraining of condensed phase and biomolecular systems, chapter 20, pp. We have recently proposed a coarsegrained model of dna that captures the basic thermodynamic, structural, and mechanical changes associated with the fundamental process in much of dna. To simulate long time and length scale processes involving dna it is necessary to use a coarse grained description. Dna nanotechnology is the design and manufacture of artificial nucleic acid structures for technological uses. Introduction to md simulation of dnaprotein systems. Coarse graining method an overview sciencedirect topics. Coarsegrained modelling of the structural properties of dna origami. Coarsegraining methods for computational biology annual. Coarsegraining dna for simulations of dna nanotechnology. Jun 01, 2016 a similar coarse graining scheme has been applied recently by naome at al who applied the inverse monte carlo approach and data from extensive allatom md simulations to determine numerically the potentials for the cg dna model in solution while testing various combinations of inter and intrastrand potentials fig.
A coarse grained model for atomicdetailed dna simulations. Insights on proteindna recognition by coarse grain modelling. Compared to dna nanostructures, rna as a nano engineering material brings additional challenging features, such as much larger diversity in tertiary structural building blocks. Smitha received xth xxxxxxxxxx 20xx, accepted xth xxxxxxxxx 20xx first published on the web xth xxxxxxxxxx 200x doi. Conformational dynamics of mechanically compliant dna nanostructures from coarse grained molecular dynamics simulations. Dna nanotechnology, specifically, is an example of bottomup molecular selfassembly, in which molecular components spontaneously organize into stable structures. It is notoriously difficult to observe, let alone control, the position and orientation of molecules due to their small size and the constant thermal fluctuations that they experience in solution. Jun 25, 2012 in the next coarsegraining step bottom, the nonbinding part of all polymers is condensed into a single soft sphere pink, while each binding sequence is condensed into a separate soft particle green. Integration the hiv dna is then carried to the cells nucleus center, where the cells dna is kept. The required simulation involves 230,000 atoms, a number that would triple if both protein and dna loops were described at the atomic level.
Coarsegraining dna for simulations of dna nanotechnology jonathan p. The basic working principle behind dna nanotechnology is the fabrication of specifically shaped nano architects in the one, two, and threedimensional 1d. In the present study, we have developed a coarse graining dna model with singlenucleotide resolution, in which potential functions for hydrogen bonds and the 7rstack effect are taken into account. The structure of dna structural motifs in the gas phase has been characterized using molecular dynamics simulations and various ion mobility spectrometry techniques. In this thesis we expand the design space of dna origami to. Coarsegrained modeling, coarsegrained models, aim at simulating the behaviour of complex systems using their coarsegrained simplified representation. Published 24 june 2010 2010 iop publishing ltd physical biology, volume 7, number 3. After introducing the coarsegrained model in the next section, we give simulation details in. In comparison to other design strategies, the dna origami nanostructures are. A good agreement between the simulated and experimental data makes the model suitable for conformational analysis of dna origami objects.
Recent examples include large ribbons 1, twodimensional lattices 2, and polyhedra 3,4, made by hybridizing systems of short strands oligonucleotides. Coarse grained modelling of the structural properties of dna origami. I then consider coarse grained models of dna, mesoscale descriptions that. Coarsegrained simulations of the selfassembly of dna linked gold nanoparticle building blocks a thesis submitted in partial fulfillment of the requirements for the degree of master of science in cell and molecular biology by charles armistead university of arkansas bachelor of science in biomedical engineering, 2014 december 2016. The field of nucleic nanotechnology1 uses dna and rna as. Aug 18, 20 to simulate long time and length scale processes involving dna it is necessary to use a coarsegrained description.
Hirerna, a recently proposed highresolution coarsegrained rna that captures many geometric details such as base pairing and stacking, is able to fold. Coarse grained modeling, coarse grained models, aim at simulating the behaviour of complex systems using their coarse grained simplified representation. We illustrate some of the range of dna nanotechnology. Lbm was also used in a study on the translocation of dna through nanopores 76 and in the calculation of rotational flow fields for dna separation simulations using streaming flow 77. Bioinspired and nano scale integrated computing edited by mary eshaghian publisher. Our current research interests fall within four main themes.
Physics dna hairs provide potential for molecular selfassembly. Md minimization, simulated annealing with restraints, and equilibration to get allatom structure smallangle x. Dna nanotweezers studied with a coarsegrained model of dna. Physical chemistry chemical physics 20, 15 47, 20395. Differentiating parallel and antiparallel dna duplexes in the.
The cg model of dna developed in the papoian laboratory uses different coarse graining of the dna without central beads and employs explicit modeling of the ionic environment but the method used for derivation of intramolecular potentials from allatom md simulations is similar to the approach used in the present work. Coarsegrained simulations of the selfassembly of dnalinked. Here we provide an overview of different approaches to such coarse graining, focussing on those at the nucleotide level that allow the selfassembly processes associated with dna nanotechnology to be studied. It provides a viable route for placing molecules and. For full access to this pdf, sign in to an existing account, or. Lbm was applied to the simulation of dna in microchannel flows to show the cross sectional lateral migration of dna induced by polymerwall hi 71 72. We use a recently developed coarsegrained model to simulate the overstretching of duplex dna. Dna nanotechnology promises to provide controllable selfassembly on the. We argue that the model can be used for efficient simulations of the structure of systems with thousands of base pairs. After the dna is unwound, but before the dna polymerase arrives, singlestranded dna binding protein ssb wraps up the ssdna to prevent the strands from annealing, protect the nucleobases from chemical modi cations and prevent the formation of hairpin structures in repetitive, selfcomplementary regions of dna 2, 5. Jun 24, 2010 coarsegraining rna nanostructures for molecular dynamics simulations. As an opensource molecular dynamics coarsegrained simulation software.
Map center of mass of the group of atoms represented by a single cg bead to that beads location 2. Generating dna origami nanostructures through shape. Coarsegraining dna for simulations of dna nanotechnology jpk doye, te ouldridge, aa louis, f romano, p sulc, c matek. Connecting the molecular world to biology requires understanding how molecularscale dynamics propagate upward in scale to define the function of biological structures. Sep 07, 2020 dna origami has emerged as a highly programmable method to construct customized objects and functional devices in the 10100 nm scale. Densely packed dna arrays exhibit hexagonal and orthorhombic local packings, as well as a weakly first order transition between them. Validation of simulations reverse coarsegraining and smallangle xray scattering reverse coarsegraining reverse coarsegraining. Dna has enormous potential as a programmable material for creating artificial nanoscale structures and devices. Multiscale method for simulating proteindna complexes. The objects structure is characterized by a 3d electron density map visualized in the figure as a surface of constant electron density. In contrast, the dna was significantly flexible, so that the structures could be gathered in four clusters.
In this tutorial, we walk through the protocol for allatom simulations of dna origami using the namd package starting from a cadnano design. Oxdna, our recentlydeveloped coarsegrained dna model, is particularly. Scaling up the size of the dna origami would enable many. Louis, flavio romano, petr sulc, christian matek, benedict e. Coarsegraining rna nanostructures for molecular dynamics. Smitha received xth xxxxxxxxxx 20xx, accepted xth xxxxxxxxx 20xx first published on the web xth xxxxxxxxxx. Oxdna, our recentlydeveloped coarsegrained dna model, is particularly suited to this task, and has opened up this field to systematic study by simulations. Molecular dynamics simulation of high density dna arrays. A a threedimensional 3d model of the pointer object built according to its idealized design. Optimizing dna nanotechnology through coarsegrained.
Multiscale coarsegrained modelling of chromatin components. Using langevindynamics simulations, several characteristics of the coarsegrained dna have been clarified. Chapman and hallcrc press, taylor and francis group, 2008. Pdf coarsegraining dna for simulations of dna nanotechnology. The field of nucleic nanotechnology 1 uses dna and rna as. Dna nanotechnology is a rapidly growing field of science that holds great promise for creating nanodevices capable of programmable transport and delivery of molecular cargoes, highprecision molecular sensing, nanomanufacturing, molecular computing, and countless other applications. In principle, allatom molecular dynamics simulations can investigate these issues, but with current computer facilities, these simulations have been limited to small rnas and to short times. Computer modeling of very large biomolecular systems, such as long dna polyelectrolytes or proteindna complexlike chromatin cannot reach allatom. Dna nanotechnology is the design and manufacture of artificial nucleic acid structures for. Cartoon of the coarsegraining process proposed by bianca mladek and coworkers for modeling metal nanoparticles coated with dna strands. Jul 26, 2006 the feasibility of the resulting multiscale modeling approach is demonstrated for a protein dna complex in which a protein called the e. Furthermore, the model reproduces the temperature dependence of the overstretching force well.
Design, optimization, and analysis of large dna and rna. In this trajectory, the e2 protein was rather rigid and remained very close to its xray counterpart. Dynamic simulation of a polymer molecule using comsol. Nanoscientists learn about and make things that are too small to see. In this field, nucleic acids are used as nonbiological engineering materials for nanotechnology rather than as the carriers of genetic information in living cells. Molecular selfassembly with dna enables building customshaped nanometerscale objects with molecular weights up to the megadalton regime.
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