RNA model introduction

2015-10-07T14:28:54Z

Sulc: /* References */

===Description of the oxRNA model===
The RNA model, oxRNA, treats each RNA nucleotide as a single rigid body with multiple interaction sites, following the coarse-graining approach adopted for the DNA model.

The nucleotides interact with the following pairwise interaction potentials:

#Backbone connectivity <math>V_{\rm backbone~}</math>,
#Excluded volume <math>V_{\rm exc~}</math>,
#Hydrogen bonding <math>V_{\rm H.B.~}</math>,
#Nearest-neighbor stacking <math>V_{\rm stack~}</math>,
#Cross-stacking in a duplex <math>V_{\rm cross~st.}</math>,
#Coaxial stacking <math>V_{\rm cx.~stack}</math>.

which are schematically illustrated in the picture:

[[Image:Image_duplex_combined_annotated.png|500px]]

===Simulation units===
The code uses units for energy, mass, length and time that are convenient for a typical system. The relationship between simulation units (SU) and SI units is given below.

{|
|-
! Simulation unit
! Physical unit
|-
| 1 unit of length
| 8.4x10<math>^{-10}</math> m
|-
| 1 unit of energy
| 4.142x10<math>^{-20}</math> J
|-
| 1 unit of temperature
| 3000 K
|-
| 1 unit of force
| 4.93x10<math>^{-11}</math> N
|-
| 1 unit of mass
| 5.34x10<math>^{-25}</math> kg
|-
| 1 unit of time
| 3.06x10<math>^{-12}</math> s
|-
|}

===Running a simulation with the oxRNA model===

The oxRNA model is integrated into the oxDNA simulation code. In particular, it is possible to use the Virtual Move Monte Carlo (VMMC), Monte Carlo (MC) and Molecular Dynamics (MD) simulation algorithms using the same format of input file as for the DNA model. The format of the configuration files is also the same as for the DNA model, described in [[Documentation]]. When running simulations of the oxRNA model, the following additional line must be included in the input file to specify that the RNA model is to be used:
<pre>
interaction_type = RNA
</pre>

The RNA model comes with two parametrizations, the average-base and sequence-dependent one. In the average-base parametrization, the <math>V_{\rm H.B.}</math> interaction strengths are the same for all Watson-Crick and wobble base pairs (AU, GC, GU) and 0 for all other types of base pairs, and the interaction strengths have the same strength for all possible pairs of nucleotides interacting with the stacking interaction <math>V_{\rm stack}</math>.
In the sequence-dependent version of the model, the interaction strengths of <math>V_{\rm stack}</math> and <math>V_{\rm H.B.}</math> depend on the type of interacting bases (interactions for <math>V_{\rm H.B.}</math> are still 0 for base pairs other than AU, GC or GU).

The average-base parametrization is used by default. In order to use the sequence-dependent version of the model, the following options need to be added into the input file:
<pre>
use_average_seq = 0
seq_dep_file = rna_sequence_dependent_parameters.txt
</pre>

Note that the file <tt>rna_sequence_dependent_parameters.txt</tt> needs to be located in the directory where you run the simulation, or the full location of the file needs to be specified in the <tt>seq_dep_file</tt> option.

Furthermore, the initial configuration files need to be generated so that the nucleotides are positioned in an arrangement that satisfies the RNA potentials (for instance in the case of a duplex, they need to be initialized in an A-helical structure). For this purpose, a script <tt>generate-RNA.py</tt> is provided in the <tt>UTILS/</tt> subdirectory of the source code main directory.
For instance, if one wants to generate an initial configuration consisting of three strands, two of them complementary (with sequence 3'-GCAAGUCG-5' and its complementary) in a duplex configuration, and one single strand with sequence 3'-ACCCGU-5', one needs to create the following text file, called for example <tt>sequences.txt</tt>:
<pre>
DOUBLE GCAAGUCG
ACCCGU
</pre>
Note that the sequences are always specified in 3'-5' order.
In order to create the initial configuration files <tt>generated.top</tt> and <tt>generated.conf</tt> with the duplex and single strand randomly placed in a simulation cube with side of length 20 in simulation units, run the script
<pre>
generate-RNA.py sequences.txt generated 20.0
</pre>

which will create the configuration files. These can then be used as an initial configuration for a simulation. Other input file options that apply to oxDNA, such external_forces=1 (for the use of external forces), can be used with oxRNA with the same syntax (see [[Documentation]] for a full list and for further details).

For an example on how to use VMMC simulations to determine the melting temperature of an RNA duplex, please see the [[RNA duplex melting]] tutorial.

The latest version of the code also includes Debye-Huckel potential for electrostatic interactions. RNA2 version of the code needs to be used if one wants to include electrostatic effects at given salt concentration. For example, to run the code at 0.5M salt concentration, include the following in the input file:
<pre>
interaction_type = RNA2
salt_concentration = 0.5
</pre>

===Visualization of RNA configurations===

In order to visualize the configurations of the oxRNA model, one can use the <tt>traj2chimera.py</tt> script, as described for the oxDNA model. It is however necessary to first set the environment variable <tt>OXRNA</tt> to 1 in order for the script to properly generate visual representation of oxRNA:
<pre>
export OXRNA=1
</pre>

The visualization of a configuration specified in, for example, <tt>generated.top</tt> and <tt>generated.conf</tt> can then be obtained by running
<pre>
traj2chimera.py generated.conf generated.top
</pre>
in the <tt>UTILS/</tt> directory
which creates the files <tt>generated.conf.pdb</tt> and <tt>chimera.com</tt> which can then be visualized with [http://www.cgl.ucsf.edu/chimera/download.html Chimera software]
by running the following command:
<pre>
chimera generated.conf.pdb chimera.com
</pre>
or alternatively, you can load <tt>generated.conf.pdb</tt> in the Chimera software and then click on Tools->General Controls->Command line and specify
<pre>
read chimera.com
</pre>
in the command line, where <tt>chimera.com</tt> needs to be present in the directory where you started Chimera.

===References===
The model and its performance is discussed in detail in the following reference:

P. Šulc, F. Romano, T. E. Ouldridge, J. P. K. Doye, A. A. Louis: [http://scitation.aip.org/content/aip/journal/jcp/140/23/10.1063/1.4881424 A nucleotide-level coarse-grained model of RNA], : The Journal of Chemical Physics 140, 235102 (2014)

The extension to include salt-dependent effects is describe in the supplementary material of the following reference:

C. Matek, P. Šulc, F. Randisi, J. P. K. Doye, A. A. Louis: [http://arxiv.org/abs/1506.02539 Coarse-grained modelling of supercoiled RNA], : The Journal of Chemical Physics (in press), (2015)

RNA model introduction

2015-10-07T14:24:07Z

Sulc:

===Description of the oxRNA model===
The RNA model, oxRNA, treats each RNA nucleotide as a single rigid body with multiple interaction sites, following the coarse-graining approach adopted for the DNA model.

The nucleotides interact with the following pairwise interaction potentials:

#Backbone connectivity <math>V_{\rm backbone~}</math>,
#Excluded volume <math>V_{\rm exc~}</math>,
#Hydrogen bonding <math>V_{\rm H.B.~}</math>,
#Nearest-neighbor stacking <math>V_{\rm stack~}</math>,
#Cross-stacking in a duplex <math>V_{\rm cross~st.}</math>,
#Coaxial stacking <math>V_{\rm cx.~stack}</math>.

which are schematically illustrated in the picture:

[[Image:Image_duplex_combined_annotated.png|500px]]

===Simulation units===
The code uses units for energy, mass, length and time that are convenient for a typical system. The relationship between simulation units (SU) and SI units is given below.

{|
|-
! Simulation unit
! Physical unit
|-
| 1 unit of length
| 8.4x10<math>^{-10}</math> m
|-
| 1 unit of energy
| 4.142x10<math>^{-20}</math> J
|-
| 1 unit of temperature
| 3000 K
|-
| 1 unit of force
| 4.93x10<math>^{-11}</math> N
|-
| 1 unit of mass
| 5.34x10<math>^{-25}</math> kg
|-
| 1 unit of time
| 3.06x10<math>^{-12}</math> s
|-
|}

===Running a simulation with the oxRNA model===

The oxRNA model is integrated into the oxDNA simulation code. In particular, it is possible to use the Virtual Move Monte Carlo (VMMC), Monte Carlo (MC) and Molecular Dynamics (MD) simulation algorithms using the same format of input file as for the DNA model. The format of the configuration files is also the same as for the DNA model, described in [[Documentation]]. When running simulations of the oxRNA model, the following additional line must be included in the input file to specify that the RNA model is to be used:
<pre>
interaction_type = RNA
</pre>

The RNA model comes with two parametrizations, the average-base and sequence-dependent one. In the average-base parametrization, the <math>V_{\rm H.B.}</math> interaction strengths are the same for all Watson-Crick and wobble base pairs (AU, GC, GU) and 0 for all other types of base pairs, and the interaction strengths have the same strength for all possible pairs of nucleotides interacting with the stacking interaction <math>V_{\rm stack}</math>.
In the sequence-dependent version of the model, the interaction strengths of <math>V_{\rm stack}</math> and <math>V_{\rm H.B.}</math> depend on the type of interacting bases (interactions for <math>V_{\rm H.B.}</math> are still 0 for base pairs other than AU, GC or GU).

The average-base parametrization is used by default. In order to use the sequence-dependent version of the model, the following options need to be added into the input file:
<pre>
use_average_seq = 0
seq_dep_file = rna_sequence_dependent_parameters.txt
</pre>

Note that the file <tt>rna_sequence_dependent_parameters.txt</tt> needs to be located in the directory where you run the simulation, or the full location of the file needs to be specified in the <tt>seq_dep_file</tt> option.

Furthermore, the initial configuration files need to be generated so that the nucleotides are positioned in an arrangement that satisfies the RNA potentials (for instance in the case of a duplex, they need to be initialized in an A-helical structure). For this purpose, a script <tt>generate-RNA.py</tt> is provided in the <tt>UTILS/</tt> subdirectory of the source code main directory.
For instance, if one wants to generate an initial configuration consisting of three strands, two of them complementary (with sequence 3'-GCAAGUCG-5' and its complementary) in a duplex configuration, and one single strand with sequence 3'-ACCCGU-5', one needs to create the following text file, called for example <tt>sequences.txt</tt>:
<pre>
DOUBLE GCAAGUCG
ACCCGU
</pre>
Note that the sequences are always specified in 3'-5' order.
In order to create the initial configuration files <tt>generated.top</tt> and <tt>generated.conf</tt> with the duplex and single strand randomly placed in a simulation cube with side of length 20 in simulation units, run the script
<pre>
generate-RNA.py sequences.txt generated 20.0
</pre>

which will create the configuration files. These can then be used as an initial configuration for a simulation. Other input file options that apply to oxDNA, such external_forces=1 (for the use of external forces), can be used with oxRNA with the same syntax (see [[Documentation]] for a full list and for further details).

For an example on how to use VMMC simulations to determine the melting temperature of an RNA duplex, please see the [[RNA duplex melting]] tutorial.

The latest version of the code also includes Debye-Huckel potential for electrostatic interactions. RNA2 version of the code needs to be used if one wants to include electrostatic effects at given salt concentration. For example, to run the code at 0.5M salt concentration, include the following in the input file:
<pre>
interaction_type = RNA2
salt_concentration = 0.5
</pre>

===Visualization of RNA configurations===

In order to visualize the configurations of the oxRNA model, one can use the <tt>traj2chimera.py</tt> script, as described for the oxDNA model. It is however necessary to first set the environment variable <tt>OXRNA</tt> to 1 in order for the script to properly generate visual representation of oxRNA:
<pre>
export OXRNA=1
</pre>

The visualization of a configuration specified in, for example, <tt>generated.top</tt> and <tt>generated.conf</tt> can then be obtained by running
<pre>
traj2chimera.py generated.conf generated.top
</pre>
in the <tt>UTILS/</tt> directory
which creates the files <tt>generated.conf.pdb</tt> and <tt>chimera.com</tt> which can then be visualized with [http://www.cgl.ucsf.edu/chimera/download.html Chimera software]
by running the following command:
<pre>
chimera generated.conf.pdb chimera.com
</pre>
or alternatively, you can load <tt>generated.conf.pdb</tt> in the Chimera software and then click on Tools->General Controls->Command line and specify
<pre>
read chimera.com
</pre>
in the command line, where <tt>chimera.com</tt> needs to be present in the directory where you started Chimera.

===References===
The model and its performance is discussed in detail in the following reference:

P. Šulc, F. Romano, T. E. Ouldridge, J. P. K. Doye, A. A. Louis: [http://scitation.aip.org/content/aip/journal/jcp/140/23/10.1063/1.4881424 A nucleotide-level coarse-grained model of RNA], : The Journal of Chemical Physics 140, 235102 (2014)

Documentation

2015-07-23T20:47:55Z

Sulc: /* Analysis of configurations */

==Compile options==

Compiling oxDNA requires that you have a working <tt>cmake</tt> software and C++ compiler on your machine. The instructions are provided in the [[Download and Installation]] section.

==Usage==

<pre>oxDNA input_file</pre>

The input file contains all the relevant information for the program to run, such as what initial configuration to use, the topology of the system, how often to print the energies to a file, etc. Please make sure you read the [[Thermostat|thermostat]] page if you use molecular dynamics.

==Input file==

As always in UNIX environments, everything is case sensitive.

*Options are in the form key = value
*There can be arbitrary spaces before and after both key and value
*Line with a leading # will be treated as comments
*The | (pipe) sign is the separator between the different values that can be used to specify a value for the key.
*Keys between [ and ] are optional, the value after the equal sign is the default value

Here we provide a list of the most commonly used input options. The complete and most up-to-date list of possible options can be found [[Input_options|here]] or in the <tt>README</tt> file in the main directory of the simulation code.

The input options of the previous oxDNA version can be found [[Input_options_of_the_previous_version|here]].

===Generic options===
The options listed here define the generic behavior of the entire program.
;[interaction_type = DNA]: DNA|DNA2|RNA|patchy|LJ
: (selects the model for the simulation. DNA ([[DNA_model_introduction|oxDNA model]]) is the default option. DNA2 ([[DNA_model_introduction#oxDNA2|oxDNA2 model]]), RNA ([[RNA_model_introduction|oxRNA model]]), LJ (Lennard-Jones) and patchy particles are also implemented
;[sim_type=MD]: MD|MC|VMMC
:MD = Molecular Dynamics, MC = Monte Carlo, VMMC = Virtual Move Monte Carlo
;backend: CPU | CUDA
: (only sim_type=MD is supported if you choose CUDA backend)
;backend_precision: float|double|mixed
: (mixed option is available only for CUDA backend. It is recommended choice for optimal performance on CUDA machines, double is recommended for CPU simulations)
;[debug=0]: 0|1
: 1 if you want verbose logs, 0 otherwise.

===Simulation options===
The options listed here specify the behaviour of the simulation.

;steps: number of steps to be performed.

;[restart_step_counter=0]: 0|1
:0 means that the step counter will start from the value read in the configuration file; if 1, the step counter will be reset to 0. The total duration of the simulation is unchanged.

;[seed=time(NULL)]: seed for the random number generator. On Unix systems, it will use by default a number from /dev/urandom + time(NULL)

;T: temperature of the simulation. It can be expressed in simulation units or kelvin (append a k or K after the value) or celsius (append a c or C after the value).
:Examples:
{|
|-
! Value
! Simulation Units
|-
| 0.1
| 0.1
|-
| 300 K
| 0.1
|-
| 300k
| 0.1
|-
| 26.85c
| 0.1
|-
| 26.85 C
| 0.1
|-
|}

;verlet_skin: if a particle moves more than verlet_skin then the lists will be updated. Its name is somewhat misleading: the actual verlet skin is 2*verlet_skin.

;salt_concentration: used if interaction_type = DNA2. It specifies the salt concentration in M.

;[use_average_seq=1]: 0|1
: specifies whether to use the default hard-coded average parameters for base-pairing and stacking interaction strengths or not. If sequence dependence is to be used, set this to 0 and specify seq_dep_file.

;[seq_dep_file]: specifies the file from which the sequence dependent parameters should be read. Mandatory if use_average_seq=no, ignored otherwise. A sample file is provided (sequence_dependent_parameters.txt).

;[external_forces=0]: 0|1
: specifies whether there are external forces acting on the nucleotides or not. If it is set to 1, then a file which specifies the external forces' configuration has to be provided (see external_forces_file).

;[external_forces_file]: specifies the file containing all the external forces' configurations. Currently there are six supported force types (see EXAMPLES/TRAPS for some examples):
:*string
:*twist
:*trap
:*repulsion_plane
:*repulsion_plane_moving
:*mutual_trap

====Molecular dynamics simulations options====

;dt: time step of the integration.

;thermostat: no|refresh|brownian
:no means no thermostat will be used. refresh will refresh all the particle's velocities from a maxwellian every newtonian_steps steps. john is an Anderson-like thermostat (see pt). Make sure you read [[Thermostat|thermostat]].

;newtonian_steps: required if thermostat != no
:number of steps after which a procedure of thermalization will be performed.

;pt: used if thermostat == john. It's the probability that a particle's velocity will be refreshed during a thermalization procedure.

;diff_coeff: required if pt is not specified
:used internally to automatically compute the pt that would be needed if we wanted such a self diffusion coefficient. Not used if pt is set.

====Monte Carlo simulations options====

;[check_energy_every=10]: this number times print_energy_every gives the number of steps after which the energy will be computed from scratch and checked against the actual value computed adding energy differences.

;[check_energy_threshold=1e-4]: if abs((old_energy - new_energy)/old_energy) > check_energy_threshold then the program will die and warn the user.

;ensemble: NVT
:ensemble of the simulation. More ensembles could be added in future versions.

;delta_translation: maximum displacement (per dimension) for translational moves in simulation units.

;delta_translation: maximum displacement for rotational moves in simulation units.

===Input/output===
The options listed here are used to manage the I/O (read and write configurations, energies and so on)

;conf_file: initial configuration file.

;topology: file containing the system's topology.

;trajectory_file: the main output of the program. All the configurations will be appended to this file as they are printed.

;[confs_to_skip=0]: valid only if conf_file is a trajectory. Skip the first confs_to_skip configurations and then load in memory the (confs_to_skip+1)th.

;[lastconf_file=last_conf.dat]: this is the file where the last configuration is saved (when the program finishes or is killed). Set to last_conf.dat by default

;[refresh_vel=0]: 0|1
:if 1 the initial velocities will be refreshed from a maxwellian.

;energy_file: energy output file.

;[print_energy_every=1000]: this will make the program print the energies every print_energy_every steps.

;[no_stdout_energy=0]: 0|1
:if 1 the energy will be printed just to the energy_file.

;[time_scale=linear]: linear|log_lin
:using linear configurations will be saved every print_conf_interval.
:using log_lin configurations will be saved logarithmically for print_conf_ppc times. After that the logarithmic sequence will restart.

;print_conf_interval: linear interval if time_scale == linear. First step of the logarithmic scale if time_scale == log_lin.

;[print_reduced_conf_every=0]: every print_reduced_conf_every steps the program will print out the reduced configurations (i.e. confs containing only the centers of mass of strands).

;reduced_conf_output_dir: used if print_reduced_conf_every > 0
:output directory for reduced_conf files.

;[log_file=stderr]: file where generic and debug informations will be logged. If not specified then stderr will be used.

==Output files==
*The log file contains all the relevant information about the simulation (specified options, activated external forces, warnings about misconfigurations, critical errors, etc.). If the log file is omitted, all this information will be displayed on the standard output.

*The energy file layout for MD simulations is

:{|
| [time (steps * dt)]
| [potential energy]
| [kinetic energy]
| [total energy]
|}

:while for MC simulations is

:{|
| [time (steps)]
| [potential energy]
| [acceptance ratio for translational moves]
| [acceptance ratio for rotational moves]
| [acceptance ratio for volume moves]
|}

:VMMC output also produces the following extra columns if umbrella sampling is enabled
:{|
|[order parameter coordinate 1]
|[order parameter coordinate 1]
|...
|[order parameter coordinate n]
|[current weight]
|}

:N.B. potential, kinetic and total energies are divided by the total number of particles.

*Configurations are saved in the trajectory file.

==Configuration and topology files==
The current state of a system, as specified by oxDNA, is described by two files: a configuration file and a topology file. The configuration file contains all the general information (timestep, energy and box size) and the orientations and positions of each nucleotide. The topology file, on the other hand, keeps track of the backbone-backbone bonds between nucleotides in the same strand. Working configuration and topology files can be found in the <tt>[[Examples|EXAMPLES]]</tt> directory.

===Configuration file===
The first three rows of a configuration file contain the timestep <tt>T</tt> at which the configuration has been printed, the length of the box sides <tt>Lx</tt>, <tt>Ly</tt> and <tt>Lz</tt> and the total, potential and kinetic energies, <tt>Etot</tt>, <tt>U</tt> and <tt>K</tt>, respectively:

<pre>
t = T
b = Lz Ly Lz
E = Etot U K
</pre>

after this header, each row contains position of the centre of mass, orientation, velocity and angular velocity of a single nucleotide in the following order:

<math>\overbrace{r_x r_y r_z}^{\rm Position} \overbrace{b_x b_y b_z}^{\rm Backbone-base versor} \overbrace{n_x n_y n_z}^{\rm Normal versor} \overbrace{v_x v_y v_z}^{\rm Velocity} \overbrace{L_x L_y L_z}^{\rm Angular velocity}</math>

===Topology file===
The topology file stores the intra-strand, fixed bonding topology (i.e. which nucleotides share backbone links). The first row contains the total number of nucleotides <tt>N</tt> and the number of strands <tt>Ns</tt>:

<pre>
N Ns
</pre>

After this header, the <tt>i</tt>-th row specifies strand, base and 3' and 5' neighbors of the <tt>i</tt>-th nucleotide in this way:

<pre>
S B 3' 5'
</pre>

where S is the index of the strand (starting from 1) which the nucleotide belongs to, B is the base and 3' and 5' specify the index of the nucleotides with which the <tt>i</tt>-th nucleotide is bonded in the 3' and 5' direction, respectively. A <tt>-1</tt> signals that the nucleotide terminates the strand in either 3' or 5' direction. The topology file of a strand of sequence <tt>GCGTTG</tt> would be:

<pre>
6 1
1 G -1 1
1 C 0 2
1 G 1 3
1 T 2 4
1 T 3 5
1 G 4 -1
</pre>

Specifying the topology in this way can simplify the process of simulating, for example, circular DNA.

===Generation of initial configurations===
In order to generate initial configuration and topology files, we provide the <tt>${oxDNA}/UTILS/generate-sa.py</tt> script. The usage of the script is

<pre>generate-sa.py <box side> <file with sequence></pre>

where <tt><box side></tt> specifies the length of the box side in simulation units and <tt><file with sequence></tt> contains the sequence of the strands to be generated, one row per strand. If double strands are needed, each sequence must be preceded by <tt>DOUBLE</tt>. For example, a file containing

<pre>
DOUBLE AGGGCT
CCTGTA
</pre>

would generate a double strand with a sequence <tt>AGGGCT</tt> and a single strand with a sequence <tt>CCTGTA</tt>. The sequences are given in 3'-5' order.

Positions and orientations of the strands are all chosen at random in such a way that the resulting initial configuration does not contain significant excluded volume interactions between nucleotides belonging to different strands. Generated single- and double-strands have helical conformations (i.e. they are in the minimum of the intra-strand interaction energy).

The output configuration and topology are stored in <tt>generated.dat</tt> and <tt>generated.top</tt>, respectively.
Since this script will initialize nucleotides' velocities and angular velocities to 0, when performing a molecular (or Brownian) dynamics simulation remember to put <tt>refresh_vel = 1</tt> in the [[Documentation#Input_file|input]] file.

==Analysis of configurations==
The configurations produced by oxDNA can be analysed with the <tt>output_bonds</tt> program in <tt>${oxDNA}/UTILS/process_data/</tt> directory. This program takes as command line arguments the input file (to recover the temperature and topology file), a configuration/trajectory file and an optional number. Since <tt>output_bonds</tt> reads analyses a single configuration, the optional number selects the configuration which it needs to analyse in the trajectory. Analysing a whole trajectory can be done by looping over a counter.

Please note that <tt>output_bonds</tt> is not compiled automatically. If you never compiled it, do so as described in the [[Download_and_Installation#Installation|installation instructions]].

<tt>output_bonds</tt> can be used as follows:
<pre>
${oxDNA}/UTILS/process_data/output_bonds <input_file> <trajectory_file> [counter]
</pre>

The program outputs some debugging information to the standard error and information regarding the interaction energies to the standard output. The contributions arising from each of the terms in the potential (see the appendix of [[Publications|Ref. 2]]) are reported for each pair of nucleotides that have non-zero total interactions.

This output can be easily parsed to analyse the configurations.

For each pair of nucleotides that do interact in the configuration, the program prints out a line containing:
* The id of the two particles (starting from 0)
* The total interaction energy
* The hydrogen bonding (base pairing) energy
* The stacking energy
* The cross stacking energy
* The excluded volume energy
* The FENE interaction energy
* A letter indicating a status code. This will be <tt>N</tt> for pairs that interact through bonded interactions (i.e. they are neighbors along a strand) and it will be <tt>H</tt> when a base pair is present. Our definition of base pair is when two nucleotides have a hydrogen bonding energy less than -0.1 in simulation units (see [[Publications|Ref. 2]]).

===Geometry of the Model===
In the configuration/trajectory files only the positions and orientations of the nucleotides are stored. If one wants to recover the positions of the individual interaction sites in the model, some maths need to be done.

The position of the base, stacking and backbone sites can be recovered as follows:

base site: (center) + 0.40 * (axis vector)

stacking site: (center) + 0.34 * (axis vector)

backbone site: (center) - 0.40 * (axis_vector)

The picture in the [[Model_introduction|introduction]] might help understanding where the sites are.

==External Forces==
The code implements several types of external forces that can be imposed on the system that can be used either to simulate tension exerted on DNA or simply to accelerate the formation of secondary or tertiary structure. External forces can be tricky to treat, especially in a dynamics simulation, since they are an external source of work. Care should be taken in adjusting the time step, thermostat parameters and such.

To enable external forces, one needs to specify <tt>external_forces = 1</tt> in the input file and also supply an external force file to read from with the key <tt>external_forces_file = <file></tt>.

The syntax of the external forces file is quite simple. Examples of such files can be found in the [[Hairpin_formation|hairpin formation]] and [[Pseudoknot|Pseudoknot formation]] examples. Each force is specified within a block contained in curly brackets. Empty lines and lines beginning with an hash symbol (<tt>#</tt>) are ignored. Different forces require different keys to be present. If the file has the wrong syntax, oxDNA should spit out a sensible error message while parsing the file.

The different types of forces implemented at the moment are:
* harmonic trap
* string
* repulsion plane
* mutual trap

All forces act on the centre of the particle.

Forces of different kinds can be combined in the same simulation. There is a maximum number of 10 external forces per particle for memory reasons. This can be manually overridden recompiling the code with a different value of the macro <tt>MAX_EXT_FORCES</tt> (currently 10) in <tt>defs.h</tt>.

===String===
A string is implemented as a force that does not depend on the particle position. Its value can be constant or can change linearly with time. It is useful as it does not fluctuate with time.

A force of this kind is specified with <tt>type = string</tt>. The relevant keys are:
* '''particle''' (int) the particle on which to exert the force
* '''F0''' (float) the value of the force at time = 0 in simulation units (please note that the value of the time may or may not be reset when starting a simulation, depending on the input file)
* '''rate''' (float) growing rate of the force (simulation units/time steps). Typical values are very small (< 10^(-5))
* '''dir''' (3 floats separated by commas) direction of the force (automatically normalised by the code)

The following bit of code will create an external force on the first nucleotide in the system starting at 1 simulation units (48.6 pN) and growing linearly with time at the rate of 48.6pN every million time steps. The force will pull the nucleotide along the <tt>z</tt> direction.

<pre>
{
type = string
particle = 0
F0 = 1.
rate = 1e-6
dir = 0., 0., 1.
}
</pre>

===Harmonic trap===
This type of force implements an harmonic trap, of arbitrary stiffness, that can move linearly with time. It can be useful to fix the position of the nucleotides to simulate attachment to something or to implement (quasi) constant extension simulations.

A force of this kind is specified with <tt>type = trap</tt>. The relevant keys are:
* '''particle''' (int) the particle on which to exert the force
* '''pos0''' (3 floats separated by commas) rest position of the trap
* '''stiff''' (float) stiffness of the trap (the force is stiff * dx)
* '''rate''' (float) speed of the trap (length simulation units/time steps)
* '''dir''' (3 floats separated by commas) direction of movement of the trap

Here is an example input for a harmonic trap acting on the third nucleotide constraining it to stay close to the origin. In this example the trap does not move (<tt>rate=0</tt>), but one could have it move at a constant speed along the direction specified by <tt>dir</tt>, in this case the <tt>x</tt> direction.

<pre>
{
type = trap
particle = 2
pos0 = 0., 0., 0.
stiff = 1.0
rate = 0.
dir = 1.,0.,0.
}
</pre>

Please note that the trap does not comply with periodic boundary conditions. This is most likely what you want.

===Repulsion plane===
This kind of external force implements a repulsion plane that constrains a particle (or the whole system) to stay on one side of it. It is implemented as a harmonic repulsion, but the stiffness can be made arbitrarily high to mimic a hard repulsion.

A force of this kind is specified with <tt>type = repulsion_plane</tt>. The relevant keys are:
* '''particle''' (int) the particle on which to exert the force. If set to the special value -1, the force will be exerted on all particles.
* '''stiff''' (float) stiffness of the trap (the force is stiff * D, where D is distance from the plane. The force is exerted only if the nucleotide is below the plane)
* '''dir''' (3 floats separated by commas) a direction normal to the plane
* '''position''' (1 float number) specifies the position of the plane

If direction is <tt> direction = u,v,w </tt> , then the plane contains all the points (x,y,z) that satisfy the equation: u*x + v*y + w*z + position = 0.
Only nucleotides with coordinates (x,y,z) that satisfy u*x + v*y + w*z + position < 0 will feel the force.
The force exerted on a nucleotide is equal to stiff * D, where D is the distance of the nucleotide from the plane, where <math> D = | ux + vy + wz + \mbox{position}| / \sqrt{u^2 + v^2 + w^2 }.</math>
For nucleotides for which u*x + v*y + w*z + position >= 0, no force will be exerted.

Here is an example. This plane acts on the whole system and will not exert any force on nucleotides with a positive <tt>x</tt> coordinate. A force proportional to 48.6 pN * (<tt>x</tt> coordinate) will be exerted on all particles .

<pre>
{
type = repulsion_plane
#whole system
particle = -1
stiff = 1. #48.6 pN /(simulation length unit)
dir = 1, 0, 0
position = 0
}
</pre>

If in the above example you would specify position = 3, then the force would be exerted on all nucleotides with coordinate x > -3.

===Mutual trap===
This force is useful to form initial configurations. It is a harmonic force that at every moment pulls a particle towards a reference particle. It is possible to specify the separation at which the force will be 0.

A force of this kind is specified with <tt>type = mutual_trap</tt>. The relevant keys are:
* '''particle''' (int) the particle on which to exert the force.
* '''ref_particle''' (int) particle to pull towards. Please note that this particle will not feel any force (the name mutual trap is thus misleading).
* '''stiff''' (float) stiffness of the trap
* '''r0''' (float) equilibrium distance of the trap.

Here is an example, extracted from the [[Pseudoknot|pseudoknot formation example]]. This will pull particle 14 towards particle 39, favouring an equilibrium distance of 1.4 (which corresponds roughly to the minimum of the hydrogen bonding potential, not a coincidence). The same force with opposite sign is exerted on particle 39 through a separate force. It is not necessary to have both particles feel the force, but it usually works much better.

<pre>
{
type = mutual_trap
particle = 14
ref_particle = 39
stiff = 1.
r0 = 1.2
}

{
type = mutual_trap
particle = 39
ref_particle = 14
stiff = 1.
r0 = 1.2
}
</pre>

==Visualisation of structures==
oxDNA produces a trajectory file where all the relevant information is
stored. A converter is provided (<tt>traj2vis.py</tt>) in the
<tt>UTILS</tt> directory that is able to produce files in the <tt>xyz</tt>
and <tt>pdb</tt> formats. The same program can be used on a configuration
file and it will produce a snapshot.

Since the model is coarse-grained, we have to "trick" the visualisers into
thinking that the interaction sites in the model are actually atoms.
Advanced nucleic acids representations such as ribbons will not work on the
outputs.

All the images in the [[Screenshots]] page were produced with the pdb representation using UCSF chimera (see later on).

===xyz format===

just run

<pre>$oxDNA/UTILS/traj2vis.py xyz <trajectory> <topology> </pre>

(where <tt>$oxDNA</tt> is the oxDNA source directory) to get the xyz representation in a file called the same as the trajectory
file with <tt>.xyz</tt> appended. Please note that boundary conditions are
implemented strand-wise, so strands that are bound might appear at two
different sizes of the box. Also, the center of mass of the system (where
each strand is weighted the same regardless of the length) is set to 0 at
each frame. Carbons represent the backbone sites and oxygens the base sites.

The resulting file can be read with a variety of programs. Here we will
explain how to visualise it sensibly in [http://www.ks.uiuc.edu/Research/vmd/ VMD].

* Run VMD and load the xyz file.
* In the graphics menu, go to Representations.
* In the Selected Atoms line, input <tt>name C</tt>. Also select Drawing method CPK, sphere scale 0.8 and Bond Radius 0.
* In the Selected Atoms line, input <tt>name O</tt>. Also select Drawing method CPK, sphere scale 0.6 and Bond Radius 0.

This should produce a ball representation of our model DNA. Bonds
automatically produced by VMD are NOT meaningful in our context.

===pdb format===
Run

<pre>$oxDNA/UTILS/traj2chimera.py <trajectory> <topology> </pre>

to produce a trajectory/configuration in the pdb format. A further file
called <tt>chimera.com</tt> will be produced (more on this later). All
comments above about periodic boundaries and centre of mass apply here as
well.

The pdb file can be visualised in VMD just like the xyz format, but a nicer
output can be produced with [http://www.cgl.ucsf.edu/chimera/ UCSF Chimera] (although only for snapshots at
the moment) as follows:

Run chimera and load the pdb file. An ugly output will be displayed.

Bring up the command line under the <tt>Tools → General Controls</tt> menu.
Input <tt>read chimera.com</tt> in the command line and press enter. You
should get a nicer visualisation with different bases in different colors,
all the covalent bonds in the right place, etc.

On large configurations, the production of ellipsoids will be extremely
slow. You can remove it by removing the line

<code>aniso scale 0.75 smoothing 4</code>

from the commands file. Loading the resulting file should be much faster.

UCSF chimera can in turn export the scene in a variety of formats.

DNA model introduction

2015-07-17T19:25:23Z

Sulc:

The model treats DNA as a string of rigid nucleotides, which interact through potentials which depend on the position and orientation of the nucleotides. The interactions are:
#Sugar-phosphate backbone connectivity,
#Excluded volume,
#Hydrogen bonding,
#Nearest-neighbour stacking,
#Cross-stacking between base-pair steps in a duplex,
#Coaxial stacking.

This interactions are illustrated below. Orientational modulations of the stacking potential encourage the bases to form coplanar stacks, the twist arising from the different length scales of the backbone separation and the optimum stacking separation. The possibility of unstacking allows single strands to be very flexible. Hydrogen bonding can occur between complementary bases when they are anti-aligned, leading to the formation of double helical structures.

http://www-thphys.physics.ox.ac.uk/people/ThomasOuldridge/Site/The_model.png

(a) Model interaction sites with their interaction ranges (the typical range of an interaction is twice the radius of the sphere shown).

(b) Representation of these interaction site in a visualisation that makes the planarity of the base clear.

(c) A duplex in this representation.

http://www-thphys.physics.ox.ac.uk/people/ThomasOuldridge/Site/interactions.png

Indication of the interactions which hold together a typical duplex. V(b.b.) indicates the phosphate-sugar backbone connectivity.

In the original model, all complementary base pairs and stacking partners interact with the same strength (there is no attractive interaction between non-complementary bases). A sequence-dependent parameterisation of the hydrogen-bonding and stacking interactions is included as an option in the code release.
The melting temperatures of a set of short DNA oligomers in the sequence-dependent coarse-grained model, compared to the melting temperatures as predicted by SantaLucia's nearest-neighbor model ([http://www.pnas.org/content/95/4/1460.full]), are available here: [http://www-thphys.physics.ox.ac.uk/people/PetrSulc/data/CG_model_Tm.txt]

The original model incorporates electrostatics only through the short-ranged excluded volume. For this reason, it is only appropriate for the study of systems at high salt concentration, when electrostatic interactions are strongly screened. It also does not incorporate the differentiation between the major and minor grooves of DNA double helices.

===oxDNA2===

A new version of the oxDNA model, called oxDNA2, has recently been released ([http://arxiv.org/abs/1504.00821]). It introduces different widths for the major and minor DNA double helical grooves (an example double helix is shown below), a new electrostatic interaction which allows DNA to be studied at salt concentrations of 0.1M and above, improved large-scale structure prediction, and differentiation between AA and TT stacking strengths.

https://dna.physics.ox.ac.uk/images/3/37/Perfect_yesmm_nopov.png

The oxDNA2 model is included in the latest release of the oxDNA code. It can be used in a very similar way to the original oxDNA model. Only a couple of lines in the input file must be added. Firstly, the following line must be included:

<pre>
interaction_type = DNA2
</pre>

In addition, the salt concentration for the simulation must be specified. For example, to run a simulation with a salt concentration of 0.5M, one should write:

<pre>
salt_concentration = 0.5
</pre>

Everything else should work in the same way as it does for the original oxDNA model.

===Simulation units===
The code uses units for energy, mass, length and time that are convenient for a typical system. The relationship between simulation units (SU) and SI units is given below.

{|
|-
! Simulation unit
! Physical unit
|-
| 1 unit of length
| 8.518x10<math>^{-10}</math> m
|-
| 1 unit of energy
| 4.142x10<math>^{-20}</math> J
|-
| 1 unit of temperature
| 3000 K
|-
| 1 unit of force
| 4.863x10<math>^{-11}</math> N
|-
| 1 unit of mass
| 5.24x10<math>^{-25}</math> kg
|-
| 1 unit of time
| 3.03x10<math>^{-12}</math> s
|-
|}

The model and its performance is discussed in detail in the following references (the thesis provides the most complete analysis):

T. E. Ouldridge, D.Phil. Thesis, University of Oxford, 2011.
[http://ora.ox.ac.uk/objects/uuid:b2415bb2-7975-4f59-b5e2-8c022b4a3719 Coarse-grained modelling of DNA and DNA self-assembly]

T. E. Ouldridge, A. A. Louis and J. P. K. Doye, J. Chem. Phys, 134, 085101 (2011)
[http://link.aip.org/link/?JCP/134/085101 Structural, mechanical and thermodynamic properties of a coarse-grained DNA model] ([http://arxiv.org/abs/arXiv:1009.4480 arXiv])

P. Šulc, F. Romano, T. E. Ouldridge, L. Rovigatti, J. P. K. Doye, A. A. Louis, ''J. Chem. Phys.'' '''137''', 135101 (2012)
[http://jcp.aip.org/resource/1/jcpsa6/v137/i13/p135101_s1 Sequence-dependent thermodynamics of a coarse-grained DNA model] ([http://arxiv.org/abs/1207.3391 arxiv])

B. E. K. Snodin, F. Randisi, M. Mosayebi, P. Šulc, J. S. Schreck, F. Romano, T. E. Ouldridge, R. Tsukanov, E. Nir, A. A. Louis, J. P. K. Doye, ''J. Chem. Phys.'' '''142''', 234901 (2015)
[http://scitation.aip.org/content/aip/journal/jcp/142/23/10.1063/1.4921957 Introducing Improved Structural Properties and Salt Dependence into a Coarse-Grained Model of DNA] ([http://arxiv.org/abs/1504.00821 arXiv])

Gallery of studied systems

2015-07-10T04:48:43Z

Sulc: /* RNA systems */

The systems studied with the oxDNA or oxRNA model with the links to the respective papers provided below:

==DNA systems==

<gallery mode="packed" widths=250px heights=180px >
Image:tweezers.png|''[http://prl.aps.org/abstract/PRL/v104/i17/e178101 DNA nanotweezers]''
Image:burntbridges.png|''[http://link.springer.com/article/10.1007%2Fs11047-013-9391-8 Burnt bridges motor]''
Image:two_foot.png|''[http://pubs.acs.org/doi/abs/10.1021/nn3058483 Two-footed DNA walker]''
Image:ss_pull.png|''[http://jcp.aip.org/resource/1/jcpsa6/v137/i13/p135101_s1 Single stranded pulling]''
Image:kissing_hairpins.png|''Kissing hairpins (studied with [http://jcp.aip.org/resource/1/jcpsa6/v136/i21/p215102_s1 the average model] and [http://jcp.aip.org/resource/1/jcpsa6/v137/i13/p135101_s1 the sequence-dependent model])''
Image:longhpin.png|''[http://jcp.aip.org/resource/1/jcpsa6/v137/i13/p135101_s1 Loop sequence effects on melting temperatures of hairpins]''
Image:sstack.png|''[http://jcp.aip.org/resource/1/jcpsa6/v137/i13/p135101_s1 Heterogeneous stacking transition in single strands]''
Image:fray.png|''[http://jcp.aip.org/resource/1/jcpsa6/v137/i13/p135101_s1 Duplex fraying]''
Image:strand_displace.png|''[http://nar.oxfordjournals.org/content/early/2013/09/07/nar.gkt801.full?sid=762d341b-b72f-4a09-9235-20ad3ef8aeed Biophysics of strand displacement]''
Image:over_stretch.png|''[http://jcp.aip.org/resource/1/jcpsa6/v138/i8/p085101_s1 Overstretching]''
Image:cruci.png|''[http://pubs.acs.org/doi/abs/10.1021/jp3080755 DNA Cruciforms]''
Image:hybridization.png|''[http://nar.oxfordjournals.org/content/early/2013/08/08/nar.gkt687 Hybridization kinetics]''
Image:plecto.png|''[http://arxiv.org/abs/1404.2869 Plectonemes]''
Image:colorato.png|''[http://pubs.acs.org/doi/abs/10.1021/nn501138w Gels made of tetravalent DNA nanostars]''
Image:DNA_nematic.png|''[http://pubs.rsc.org/en/content/articlehtml/2012/sm/c2sm25845e Nematic phases formed by short DNA duplexes]''
</gallery>

==RNA systems==
<gallery mode="packed" widths=250px heights=180px >
Image:pseudo.png|''[http://arxiv.org/abs/1403.4180 Pseudoknot folding thermodynamics]''
Image:khp.png|''[http://arxiv.org/abs/1403.4180 Kissing complex]''
Image:nanoring.png|''[http://arxiv.org/abs/1403.4180 Nanoring]''
Image:unzip.png|''[http://arxiv.org/abs/1403.4180 Hairpin unzipping]''

</gallery>

Gallery of studied systems

2015-07-08T20:30:24Z

Sulc: /* DNA systems */

The systems studied with the oxDNA or oxRNA model with the links to the respective papers provided below:

==DNA systems==

<gallery mode="packed" widths=250px heights=180px >
Image:tweezers.png|''[http://prl.aps.org/abstract/PRL/v104/i17/e178101 DNA nanotweezers]''
Image:burntbridges.png|''[http://link.springer.com/article/10.1007%2Fs11047-013-9391-8 Burnt bridges motor]''
Image:two_foot.png|''[http://pubs.acs.org/doi/abs/10.1021/nn3058483 Two-footed DNA walker]''
Image:ss_pull.png|''[http://jcp.aip.org/resource/1/jcpsa6/v137/i13/p135101_s1 Single stranded pulling]''
Image:kissing_hairpins.png|''Kissing hairpins (studied with [http://jcp.aip.org/resource/1/jcpsa6/v136/i21/p215102_s1 the average model] and [http://jcp.aip.org/resource/1/jcpsa6/v137/i13/p135101_s1 the sequence-dependent model])''
Image:longhpin.png|''[http://jcp.aip.org/resource/1/jcpsa6/v137/i13/p135101_s1 Loop sequence effects on melting temperatures of hairpins]''
Image:sstack.png|''[http://jcp.aip.org/resource/1/jcpsa6/v137/i13/p135101_s1 Heterogeneous stacking transition in single strands]''
Image:fray.png|''[http://jcp.aip.org/resource/1/jcpsa6/v137/i13/p135101_s1 Duplex fraying]''
Image:strand_displace.png|''[http://nar.oxfordjournals.org/content/early/2013/09/07/nar.gkt801.full?sid=762d341b-b72f-4a09-9235-20ad3ef8aeed Biophysics of strand displacement]''
Image:over_stretch.png|''[http://jcp.aip.org/resource/1/jcpsa6/v138/i8/p085101_s1 Overstretching]''
Image:cruci.png|''[http://pubs.acs.org/doi/abs/10.1021/jp3080755 DNA Cruciforms]''
Image:hybridization.png|''[http://nar.oxfordjournals.org/content/early/2013/08/08/nar.gkt687 Hybridization kinetics]''
Image:plecto.png|''[http://arxiv.org/abs/1404.2869 Plectonemes]''
Image:colorato.png|''[http://pubs.acs.org/doi/abs/10.1021/nn501138w Gels made of tetravalent DNA nanostars]''
Image:DNA_nematic.png|''[http://pubs.rsc.org/en/content/articlehtml/2012/sm/c2sm25845e Nematic phases formed by short DNA duplexes]''
</gallery>

==RNA systems==
<gallery mode="packed-overlay" widths=250px heights=180px >
Image:pseudo.png|''[http://arxiv.org/abs/1403.4180 Pseudoknot folding thermodynamics]''
Image:khp.png|''[http://arxiv.org/abs/1403.4180 Kissing complex]''
Image:nanoring.png|''[http://arxiv.org/abs/1403.4180 Nanoring]''
Image:unzip.png|''[http://arxiv.org/abs/1403.4180 Hairpin unzipping]''

</gallery>

File:Cover5.jpg

2015-07-08T03:52:14Z

Sulc: JCP cover

JCP cover

File:Cover4.jpg

2015-07-08T03:49:41Z

Sulc:

Gallery of Journal Covers

2015-07-08T03:45:42Z

2015-02-11T18:53:13Z

Sulc:

The authors of the code can be contacted at the following addresses:

*Thomas Ouldridge: t(dot)ouldridge1(at)physics(dot)ox(dot)ac(dot)uk

*[http://www-thphys.physics.ox.ac.uk/people/PetrSulc/ Petr Šulc]: psulc(at)rockefeller(dot)edu 
Center for Studies in Physics and Biology, The Rockefeller University, 1230 York Avenue, NY 10065, USA


*Flavio Romano: flavio(dot)romano(at)chem(dot)ox(dot)ac(dot)uk 
Physical and Theoretical Chemistry Laboratory, Department of Chemistry, University of Oxford, South Parks Road, Oxford, OX1 3QZ, United Kingdom


*[http://homepage.univie.ac.at/lorenzo.rovigatti/ Lorenzo Rovigatti] lorenzo(dot)rovigatti(at)univie(dot)ac(dot)at 

Faculty of Computational Physics, University of Vienna (Austria)


If you have a question about the installation or usage of the oxDNA code, you can post it to the [http://sourceforge.net/p/oxdna/discussion/ Discussion forum] at sourceforge.net, where our project is hosted.

Contact information

2015-02-11T18:52:45Z

2014-08-21T15:56:49Z

Sulc: /* Referencing */

oxDNA is free software; you can redistribute it and/or modify it under the terms of the GNU General Public License as published by the Free Software Foundation; either version 3 of the License, or (at your option) any later version.

This program is distributed in the hope that it will be useful, but WITHOUT ANY WARRANTY; without even the implied warranty of MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the GNU General Public License for more details.

You should have received a copy of the GNU General Public License along with this program; if not, write to the Free Software Foundation, Inc., 59 Temple Place - Suite 330, Boston, MA 02111-1307, USA. You can also find it on the GNU web site:

[http://www.gnu.org/copyleft/gpl.html http://www.gnu.org/copyleft/gpl.html]

A copy of the GNU General Public License version 3 can be found in the [[Download_and_Installation#Download|source]] tarball.

==Referencing==
We kindly ask you to reference oxDNA and its authors in any publication for which oxDNA was used. Since you are not legally required to do so, it is up to your common sense to decide whether you want to comply with this request or not.

You can cite us in this way:

*P. Šulc, F. Romano, T. E. Ouldridge, L. Rovigatti, J. P. K. Doye, A. A. Louis, ''J. Chem. Phys.'' '''137''', 135101 (2012)

or, if you use [http://en.wikipedia.org/wiki/BibTeX BibTeX],

<pre>
@Article{oxDNA,
author = {Petr \v{S}ulc and Flavio Romano and Thomas E. Ouldridge and Lorenzo Rovigatti and Jonathan P. K. Doye and Ard A. Louis},
title = {Sequence-dependent thermodynamics of a coarse-grained DNA model},
publisher = {AIP},
year = {2012},
journal = {The Journal of Chemical Physics},
volume = {137},
number = {13},
eid = {135101},
numpages = {14},
pages = {135101},
keywords = {biology computing; DNA; melting point; molecular biophysics; molecular configurations; thermodynamics},
url = {http://link.aip.org/link/?JCP/137/135101/1},
doi = {10.1063/1.4754132}
}
</pre>

and, if you use the oxRNA model as well, please also cite

P. Šulc, F. Romano, T. E. Ouldridge, J. P. K. Doye, A. A. Louis: A nucleotide-level coarse-grained model of RNA, ''J. Chem. Phys.'' '''140''', 235102 (2014)

<pre>
@Article{oxRNA,
author = "\v{S}ulc, Petr and Romano, Flavio and Ouldridge, Thomas E. and Doye, Jonathan P. K. and Louis, Ard A.",
title = "A nucleotide-level coarse-grained model of RNA",
journal = "The Journal of Chemical Physics",
year = "2014",
volume = "140",
number = "23",
eid = 235102,
}
</pre>

Contact information

2014-07-04T14:31:29Z

Sulc:

The authors of the code can be contacted at the following addresses:

*Thomas Ouldridge: t(dot)ouldridge1(at)physics(dot)ox(dot)ac(dot)uk

*[http://www-thphys.physics.ox.ac.uk/people/PetrSulc/ Petr Šulc]: p(dot)sulc1(at)physics(dot)ox(dot)ac(dot)uk 
Rudolf Peierls Centre for Theoretical Physics,
University of Oxford, 1 Keble Road, Oxford, OX1 3NP, United Kingdom 

*Flavio Romano: flavio(dot)romano(at)chem(dot)ox(dot)ac(dot)uk 
Physical and Theoretical Chemistry Laboratory, Department of Chemistry, University of Oxford, South Parks Road, Oxford, OX1 3QZ, United Kingdom


*[http://homepage.univie.ac.at/lorenzo.rovigatti/ Lorenzo Rovigatti] lorenzo(dot)rovigatti(at)univie(dot)ac(dot)at 

Faculty of Computational Physics, University of Vienna (Austria)


If you have a question about the installation or usage of the oxDNA code, you can post it to the [http://sourceforge.net/p/oxdna/discussion/ Discussion forum] at sourceforge.net, where our project is hosted.

License and Copyright

2014-06-16T14:52:20Z

License and Copyright

2014-06-16T13:50:43Z

Sulc:

oxDNA is free software; you can redistribute it and/or modify it under the terms of the GNU General Public License as published by the Free Software Foundation; either version 3 of the License, or (at your option) any later version.

This program is distributed in the hope that it will be useful, but WITHOUT ANY WARRANTY; without even the implied warranty of MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the GNU General Public License for more details.

You should have received a copy of the GNU General Public License along with this program; if not, write to the Free Software Foundation, Inc., 59 Temple Place - Suite 330, Boston, MA 02111-1307, USA. You can also find it on the GNU web site:

[http://www.gnu.org/copyleft/gpl.html http://www.gnu.org/copyleft/gpl.html]

A copy of the GNU General Public License version 3 can be found in the [[Download_and_Installation#Download|source]] tarball.

==Referencing==
We kindly ask you to reference oxDNA and its authors in any publication for which oxDNA was used. Since you are not legally required to do so, it is up to your common sense to decide whether you want to comply with this request or not.

You can cite us in this way:

*P. Šulc, F. Romano, T. E. Ouldridge, L. Rovigatti, J. P. K. Doye, A. A. Louis, ''J. Chem. Phys.'' '''137''', 135101 (2012)

or, if you use [http://en.wikipedia.org/wiki/BibTeX BibTeX],

<pre>
@Article{oxDNA,
author = {Petr \v{S}ulc and Flavio Romano and Thomas E. Ouldridge and Lorenzo Rovigatti and Jonathan P. K. Doye and Ard A. Louis},
title = {Sequence-dependent thermodynamics of a coarse-grained DNA model},
publisher = {AIP},
year = {2012},
journal = {The Journal of Chemical Physics},
volume = {137},
number = {13},
eid = {135101},
numpages = {14},
pages = {135101},
keywords = {biology computing; DNA; melting point; molecular biophysics; molecular configurations; thermodynamics},
url = {http://link.aip.org/link/?JCP/137/135101/1},
doi = {10.1063/1.4754132}
}
</pre>

and, if you use the oxRNA model as well, please also cite

P. Šulc, F. Romano, T. E. Ouldridge, J. P. K. Doye, A. A. Louis: A nucleotide-level coarse-grained model of RNA, ''arXiv preprint: arXiv:1403.4180'' (2014)

<pre>
@Article{oxRNA,
author = "Šulc, Petr and Romano, Flavio and Ouldridge, Thomas E. and Doye, Jonathan P. K. and Louis, Ard A.",
title = "A nucleotide-level coarse-grained model of RNA",
journal = "The Journal of Chemical Physics",
year = "2014",
volume = "140",
number = "23",
eid = 235102,
}
</pre>

RNA duplex melting

2014-06-14T15:38:02Z

Sulc: /* Data evaluation and estimation of the melting temperature */

[[Category:Examples]]
==Introduction==

[[Image:Melting.png|500px|thumb|A duplex and a dissociated RNA 8-mer. The VMMC simulation samples transition between duplex and single stranded states]]
This example shows how our code can be used to calculate the melting temperature of an RNA duplex (8-mer) using the Virtual Move Monte Carlo (VMMC) algorithm.
The corresponding files are located in the repository in the subdirectory <tt>EXAMPLES/RNA_DUPLEX_MELT</tt> of our source code structure.
However, the VMMC script options are the same for both oxDNA and oxRNA and the following example of setting weights, order parameters and evaluation of data produced from the VMMC simulation applies equally to the DNA model as well.

==Setting the order parameters and weights==
The example uses umbrella sampling in order to make the sampling more efficient. In order to obtain a correct estimate
of the melting temperature, the simulation has to sample the transitions between unbonded and bonded states many times.
The sampling is aided by assigning weights to a particular state, specified for this example in the file <tt> wfile.txt </tt>, where the first column specifies the value of the order parameter
(the number of native bonds in the duplex in our case) and the second column specifies the weight assigned to the state. The larger the weight, the more likely the simulation is to visit the desired state. A file specifying the weights (<tt>wfile.txt</tt>) might look like
<pre>
0 8.
1 16204
2 1882.94
3 359.746
4 52.5898
5 15.0591
6 7.21252
7 2.2498
8 2.89783
</pre>
The weights are typically chosen first by an educated guess, and then by running the simulations and adapting the weights manually to ensure that all the relevant states are sampled.
The order parameter, which in this case measures the number of native base pairs formed in an 8-mer, is specified in a file which in our example is called <tt>op.txt</tt>:
<pre>
{
order_parameter = bond
name = all_native_bonds
pair1 = 0, 15
pair2 = 1, 14
pair3 = 2, 13
pair4 = 3, 12
pair5 = 4, 11
pair6 = 5, 10
pair7 = 6, 9
pair8 = 7, 8
}
</pre>
This file specifies which base pairs count towards the order parameter. In our example, it specifies all native base pairs. The nucleotides are numbered from 0 to N-1, where N is the total number of nucleotides in the simulation. In our example, we have two complementary strands with eight nucleotides each, so we have sixteen nucleotides in total. The nucleotides are numbered from the 3' end to the 5' end, so the first 3' nucleotide of the first strand (with index 0) is complementary to the first 5' nucleotide on the second strand (which has index 15). The system can have between 0 and 8 bonds inclusive formed, and for each possible value of the order parameter, a corresponding weight is assigned in the <tt>wfile.txt</tt>.

We need to specify the path to the weight file and order parameter file in the <tt>input</tt> file, which is done by including the following options:
<pre>
op_file = op.txt
weights_file = wfile.txt
</pre>

The program will now count the amount of time the simulation spends at each value of the order parameter (i.e. how much time the simulation spends in states with 0 native bonds, 1 native bond, ..., 8 native bonds).
In order to be able to calculate the melting temperature, one is interested in the ratio of the number states where the system is in the duplex state (i.e. has at least 1 bond) and the number of states
when the system has 0 bonds. We also need to know this ratio for a range of temperatures, so that we can interpolate them and find when the yield is 0.5, which is the definition of melting temperature. We note that in the calculation of the yield, finite size effects have to be taken into account (see the discussion in [[http://iopscience.iop.org/0953-8984/22/10/104102 this paper]] for details).
One possibility is to run a series of simulations, each at a different temperature. However, it is more efficient to use histogram reweighting in order to calculate the respective yields at different temperatures by extrapolating the distribution of states visited in one simulation. This is achieved by specifying
<pre>
extrapolate_hist = 52C, 54C, 56C, 58C, 60C, 62C, 64C, 66C, 68C, 70C
</pre>
in the <tt>input</tt> file. Now, the algorithm will use histogram reweighting to extrapolate the number of occupied states to the specified temperatures.

Note that since this example concerns RNA duplexes, the <tt>input</tt> file also contains the option
<pre>
interaction_type = RNA
</pre>
and the initial configurations for this example were generated with <tt>generate-RNA.py</tt> script, as described in the [[RNA model introduction]] section.

==Data evaluation and estimation of the melting temperature==
The simulation, after executing
<pre>
oxDNA input
</pre>
will produce, among other files, <tt>last_hist.dat</tt>. Note that the values of the order parameter are printed out in the <tt>energy.dat</tt> file during the simulation. The contents of the <tt>last_hist.dat</tt> file are regularly updated during the course of the simulation (the values are updated with each simulation step, but only saved to the hard-drive as often as specified by the <tt>print_conf</tt> option).
Note that the simulation needs to run long enough to properly sample the transitions between all the states. For the case of an 8-mer, one needs at least about <math>10^9</math> iterations with the appropriate weights in order to estimate the melting temperature within 1-2K precision.
An example of the contents of the <tt>last_hist.dat</tt> file is
<pre>
#t = 800000000; extr. Ts: 0.108383 0.10905 0.109717 0.110383 0.11105 0.111717 0.112383 0.11305 0.113717 0.114383
0 7.82092e+09 9.77615e+08 1.65144e+10 9.03838e+09 5.04243e+09 2.86621e+09 1.65915e+09 9.77615e+08 5.86057e+08 3.57265e+08 2.21364e+08 1.39341e+08
1 1.14272e+08 7052.11 146764 76907.7 41117.3 22416.8 12456.8 7052.11 4065.34 2385.22 1423.65 863.974
2 6.08557e+07 32319.5 1.18642e+06 555020 264888 128915 63949.7 32319.5 16633.5 8713.56 4644.05 2517.02
3 9.12706e+07 253708 1.56321e+07 6.5964e+06 2.83907e+06 1.24575e+06 557034 253708 117652 55524.5 26656.4 13012.5
4 1.13301e+08 2.15444e+06 2.16511e+08 8.29258e+07 3.23788e+07 1.28829e+07 5.22111e+06 2.15444e+06 904787 386567 167955 74178.8
5 2.53979e+08 1.68655e+07 2.68639e+09 9.39074e+08 3.34511e+08 1.21377e+08 4.48457e+07 1.68655e+07 6.45377e+06 2.51192e+06 994075 399852
6 7.74418e+08 1.07371e+08 2.68578e+10 8.58849e+09 2.79688e+09 9.27231e+08 3.12831e+08 1.07371e+08 3.74782e+07 1.32996e+07 4.79646e+06 1.75748e+06
7 1.03628e+09 4.60608e+08 1.75626e+11 5.16622e+10 1.54698e+10 4.71386e+09 1.46119e+09 4.60608e+08 1.4761e+08 4.80752e+07 1.59081e+07 5.34659e+06
8 2.5904e+09 8.93909e+08 5.0908e+11 1.38277e+11 3.82229e+10 1.07489e+10 3.07421e+09 8.93909e+08 2.64187e+08 7.93341e+07 2.41997e+07 7.49618e+06
</pre>

Where the first line specifies the simulation time at which the file was saved and the temperatures to which the states were extrapolated (specified in simulation units; they correspond to the ones specified in the <tt>extrapolate_hist</tt> option).
The first column specifies the value of the order parameter (from 0 to 8 in our example) and the second column specifies the number of iterations that the simulation spent in that state. Note that the simulation is biased, i.e. some states are more likely to be visited because they have larger weights.
The third column shows the unbiased number of states for each value of the order parameter, which is obtained by dividing the number in the second column by the weight assigned to that order parameter value. The fourth and further columns correspond to the unbiased number of states extrapolated to the respective temperatures. From the ratios of the number of bonded states (1 to 8 bonds) to the number of unbonded states (0 bonds), one can calculate the yields at the respective temperatures and obtain the melting temperature by interpolating them and finding for the temperature at which the yield is 0.5. For convenience, a script is provided to do the interpolation:
<pre>
estimate_Tm.py last_hist.dat
</pre>
The output, for the example <tt>last_hist.dat</tt> specified above, is
<pre>
52.00 0.9774084 0.8590862
54.00 0.9566703 0.8086249
56.00 0.9185418 0.7432626
58.00 0.8521952 0.6613256
60.00 0.7470068 0.5632429
62.00 0.6024042 0.4531267
64.00 0.4380124 0.3397566
66.00 0.2868094 0.2352155
68.00 0.1723566 0.1503401
70.00 0.0977175 0.0897356
## Tm = 61.1492313255
</pre>

Where the first column specifies the temperature, the second column is the yield of duplexes in the simulation box and the third column is the finite-size-effect corrected yield of duplexes. The melting temperature corresponds to the yield (with finite-size correction) equal to 0.5. The simulation box (linear) size of 20 simulation length units corresponds to a strand concentration of 3.5x10<math>^{-4}</math>M.

File:Nanoring.png

2014-05-09T14:27:33Z

Sulc: uploaded a new version of "File:Nanoring.png"

Screenshots and movies

2014-05-09T12:38:01Z

Sulc:

=== single-stranded DNA ===
[[Image:image_ssdna.png]]

=== double-stranded DNA ===
[[Image:image_dsdna.png]]

=== Plectoneme formation ===
https://pbs.twimg.com/media/Bk7P2EqCEAAz3Yk.png

See also the following movies:

{{#ev:youtube|Njpp_DWAhBg}}

{{#ev:youtube|3GusNEYkRM4}}

=== DNA cage ===
[[Image:chiral474.png]]

=== DNA tetrahedron (double sides) ===
[[Image:tetrahedron_large.png]]

=== DNA tetrahedron ===
http://www-thphys.physics.ox.ac.uk/people/PetrSulc/images/image.png

=== DNA tile ===
[[Image:3tile.png]]

===Formation of a duplex in the simulation box ===
{{#ev:youtube|9S85iI9IYB4}}

=== Strand displacement ===
http://www-thphys.physics.ox.ac.uk/people/PetrSulc/images/stateB.png
Invading strand attached by toehold

http://www-thphys.physics.ox.ac.uk/people/PetrSulc/images/stateC.png
Invading and victim strands that are not coaxially stacked

http://www-thphys.physics.ox.ac.uk/people/PetrSulc/images/stateX.png
Invading and victim strands that are coaxially stacked

A movie of part of the strand displacement process. It shows the invading strand attached by toehold and then displacing several base pairs of the victim strand:

{{#ev:youtube|l2frV1Gd830}}

=== DX tile ===
http://www-thphys.physics.ox.ac.uk/people/PetrSulc/images/tilechimera.png

=== Kissing hairpin ===
[[Image:hairpin_kiss2.png]]

2014-05-09T12:35:12Z

Sulc:

=== single-stranded DNA ===
[[Image:image_ssdna.png]]

=== double-stranded DNA ===
[[Image:image_dsdna.png]]

=== Plectoneme formation ===
https://pbs.twimg.com/media/Bk7P2EqCEAAz3Yk.png

See also the following movies:

{{#ev:youtube|Njpp_DWAhBg}}

{{#ev:youtube|3GusNEYkRM4}}

=== DNA cage ===
[[Image:chiral474.png]]

=== DNA tetrahedron (double-stranded sides) ===
[[Image:tetrahedron_large.png]]

=== DNA tetrahedron ===
http://www-thphys.physics.ox.ac.uk/people/PetrSulc/images/image.png

===Formation of a duplex in the simulation box ===
{{#ev:youtube|9S85iI9IYB4}}

=== Strand displacement ===
http://www-thphys.physics.ox.ac.uk/people/PetrSulc/images/stateB.png
Invading strand attached by toehold

http://www-thphys.physics.ox.ac.uk/people/PetrSulc/images/stateC.png
Invading and victim strands that are not coaxially stacked

http://www-thphys.physics.ox.ac.uk/people/PetrSulc/images/stateX.png
Invading and victim strands that are coaxially stacked

A movie of part of the strand displacement process. It shows the invading strand attached by toehold and then displacing several base pairs of the victim strand:

{{#ev:youtube|l2frV1Gd830}}

=== DX tile ===
http://www-thphys.physics.ox.ac.uk/people/PetrSulc/images/tilechimera.png

=== Kissing hairpin ===
[[Image:hairpin_kiss2.png]]