Coarse-grained modelling of supercoiled RNA

We study the behaviour of double-stranded RNA under twist and tension using oxRNA, a recently developed coarse-grained model of RNA. Introducing explicit salt-dependence into the model allows us to directly compare our results to data from recent single-molecule experiments. The model reproduces extension curves as a function of twist and stretching force, including the buckling transition and the behaviour of plectoneme structures. For negative supercoiling, we predict denaturation bubble formation in plectoneme end-loops, suggesting preferential plectoneme localisation in weak base sequences. OxRNA exhibits a positive twist-stretch coupling constant, in agreement with recent experimental observations.Comment: 8 pages + 5 pages Supplementary Materia

Introducing improved structural properties and salt dependence into a coarse-grained model of DNA

We introduce an extended version of oxDNA, a coarse-grained model of deoxyribonucleic acid (DNA) designed to capture the thermodynamic, structural, and mechanical properties of single- and double-stranded DNA. By including explicit major and minor grooves and by slightly modifying the coaxial stacking and backbone-backbone interactions, we improve the ability of the model to treat large (kilobase-pair) structures, such as DNA origami, which are sensitive to these geometric features. Further, we extend the model, which was previously parameterised to just one salt concentration ([Na +] = 0.5M), so that it can be used for a range of salt concentrations including those corresponding to physiological conditions. Finally, we use new experimental data to parameterise the oxDNA potential so that consecutive adenine bases stack with a different strength to consecutive thymine bases, a feature which allows a more accurate treatment of systems where the flexibility of single-stranded regions is important. We illustrate the new possibilities opened up by the updated model, oxDNA2, by presenting results from simulations of the structure of large DNA objects and by using the model to investigate some salt-dependent properties of DNA

Theory and simulation of twisted DNA duplexes

We use basic statistical mechanics and computer simulations with coarse-grained models to investigate the response of (inhomogeneous) DNA duplexes to linear and torsional mechanical stress. While the response of homogeneous DNA to more modest external stresses has been studied in detail, much less is know about DNA response to very strong over or under twisting, or about the biologically relevant case of inhomogeneous DNA under external torsion. By simulating geometries that resemble single-molecule molecular tweezers experiments previously reported in the literature, we validate our basic models, and measure the end-to-end duplex extension, torque, and the denaturation states of individual base-pairs, as well as the position of plectonemes when present in the post-buckling state. We generalise previous observations that plectonemes are preferentially localised (i.e. pinned) on sequence mismatches to predict that any sequence that is either significantly more bent or more flexible than the rest of the duplex should present a similar effect. We develop a simple theory to quantify this preference and test it in simulations, observing a semi-quantitative agreement. We also propose a general protocol to extend the popular oxDNA coarse-grained model of DNA to treat such bent/flexible sequences, and apply it to model thymine dimers, the most common DNA photoproducts. The theory provides almost quantitative agreement with simulations; in particular, the prediction that the pinning is dependent only on the bending angle and flexibility of the sequence, but not on the detail of how these are generated, is confirmed. Some consequences of the presence of a thymine dimer in biological DNA are also proposed. Finally, we use oxDNA to investigate the boundaries between the pre-buckling, post-buckling, and torsionally melted states, as well as the features of torsionally-melted underwound and overwound DNA, respectively called L-DNA and P-DNA. Unexpectedly, we observe that both torsionally-melted forms preferentially relax writhe by forming solenoids, rather than plectonemes. We compare our results with previous experimental and theoretical work and propose some experiments to confirm or deny this peculiar feature.</p

Theory and simulation of twisted DNA duplexes

We use basic statistical mechanics and computer simulations with coarse-grained models to investigate the response of (inhomogeneous) DNA duplexes to linear and torsional mechanical stress. While the response of homogeneous DNA to more modest external stresses has been studied in detail, much less is know about DNA response to very strong over or under twisting, or about the biologically relevant case of inhomogeneous DNA under external torsion. By simulating geometries that resemble single-molecule molecular tweezers experiments previously reported in the literature, we validate our basic models, and measure the end-to-end duplex extension, torque, and the denaturation states of individual base-pairs, as well as the position of plectonemes when present in the post-buckling state. We generalise previous observations that plectonemes are preferentially localised (i.e. pinned) on sequence mismatches to predict that any sequence that is either significantly more bent or more flexible than the rest of the duplex should present a similar effect. We develop a simple theory to quantify this preference and test it in simulations, observing a semi-quantitative agreement. We also propose a general protocol to extend the popular oxDNA coarse-grained model of DNA to treat such bent/flexible sequences, and apply it to model thymine dimers, the most common DNA photoproducts. The theory provides almost quantitative agreement with simulations; in particular, the prediction that the pinning is dependent only on the bending angle and flexibility of the sequence, but not on the detail of how these are generated, is confirmed. Some consequences of the presence of a thymine dimer in biological DNA are also proposed. Finally, we use oxDNA to investigate the boundaries between the pre-buckling, post-buckling, and torsionally melted states, as well as the features of torsionally-melted underwound and overwound DNA, respectively called L-DNA and P-DNA. Unexpectedly, we observe that both torsionally-melted forms preferentially relax writhe by forming solenoids, rather than plectonemes. We compare our results with previous experimental and theoretical work and propose some experiments to confirm or deny this peculiar feature.</p

High-functionality star-branched macromolecules: Polymer size and virial coefficients

We perform high-statistics Monte Carlo simulations of a lattice model to compute the radius of gyration R-g, the center-to-end distance, the monomer distribution, and the second and third virial coefficients of star polymers for a wide range of functionalities f, 6 infinity. Structural results are finally compared with the predictions of the Daoud-Cotton model. It turns out that the blob picture of a star polymer is essentially correct up to the corona radius R-c, which depends on f and which varies from 0.7R(g) for f = 6 to 1.0R(g) for f = 40. The outer region (r > R-c), in which the monomer distribution decays exponentially, shrinks as f increases, but it does not disappear in the scaling regime even in the limit f -> infinity. We also consider the Daoud-Cotton scaling relation R-g(2) similar to f(1-nu)L(2 nu), which is found to hold only for f >> 100. (C) 2013 AIP Publishing LLC

Thermodynamics of star polymer solutions: A coarse-grained study

We consider a coarse-grained (CG) model with pairwise interactions, suitable to describe low-density solutions of star-branched polymers of functionality f. Each macromolecule is represented by a CG molecule with (f + 1) interaction sites, which captures the star topology. Potentials are obtained by requiring the CG model to reproduce a set of distribution functions computed in the microscopic model in the zero-density limit. Explicit results are given for f = 6, 12, and 40. We use the CG model to compute the osmotic equation of state of the solution for concentrations c such that Φp = c/c∗ = 1, where c∗ is the overlap concentration. We also investigate in detail the phase diagram for f = 40, identifying the boundaries of the solid intermediate phase. Finally, we investigate how the polymer size changes with c. For Φp less than 0.3, polymers become harder as f increases at fixed reduced concentration c/c∗. On the other hand, for Φp larger than 0.3, polymers show the opposite behavior:At fixed Φp, the larger the value of f, the larger their size reduction is

lorenzo-rovigatti/oxDNA: v. 3.6.0

&lt;p&gt;This release includes support for a new &lt;a href="https://lorenzo-rovigatti.github.io/oxDNA/configurations.html#new-format-5-to-3"&gt;topology file format&lt;/a&gt; and a new interaction that can simulate DNA/RNA hybrids.&lt;/p&gt; &lt;ul&gt; &lt;li&gt;Add 6 more tests to the &lt;code&gt;run&lt;/code&gt; level; these tests use the new topology and check that the DNA, RNA and NA interactions compute the right energies for a short nicked duplex&lt;/li&gt; &lt;li&gt;Add support for a &quot;new&quot; topology format where nucleotides are listed in the 5' -&gt; 3' order, which is the standard in the community&lt;/li&gt; &lt;li&gt;Add the NA interaction, which can be used to simulated hybrid DNA/RNA systems (by @eryykr, see #68 )&lt;/li&gt; &lt;li&gt;Add a old&lt;-&gt;new topology converter to the &lt;code&gt;utils&lt;/code&gt; folder&lt;/li&gt; &lt;li&gt;Add an option &lt;code&gt;stiff_rate&lt;/code&gt; to the &lt;code&gt;mutual_trap&lt;/code&gt; force&lt;/li&gt; &lt;li&gt;Remove a few warnings when compiling with CUDA&lt;/li&gt; &lt;li&gt;Fix the computation of the stress tensor on the GPU&lt;/li&gt; &lt;/ul&gt; &lt;h2&gt;oxpy&lt;/h2&gt; &lt;ul&gt; &lt;li&gt;Update pybind version from 2.2 to 2.11 to make oxpy compatible with Python 3.11&lt;/li&gt; &lt;li&gt;Deprecate support for Python versions &lt; 3.8 (see &lt;a href="https://lorenzo-rovigatti.github.io/oxDNA/install.html#using-oxpy-with-old-python-versions"&gt;here&lt;/a&gt; if an older version is still needed)&lt;/li&gt; &lt;li&gt;Add (undocumented) support for &lt;code&gt;-Dpython=On&lt;/code&gt; and &lt;code&gt;-DPYTHON=On&lt;/code&gt;&lt;/li&gt; &lt;/ul&gt; &lt;h2&gt;oat&lt;/h2&gt; &lt;ul&gt; &lt;li&gt;Add support for the new topology format&lt;/li&gt; &lt;li&gt;Fixed an error in the oxDNA_PDB CLI parser&lt;/li&gt; &lt;li&gt;Added error handling for truncated trajectories in the oat parser (see #67)&lt;/li&gt; &lt;/ul&gt