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.. sidebar:: Software Technical Information
Name
OpenMM_Plectoneme
Language
Python 3.7, OpenMM API
Licence
`MIT <https://opensource.org/licenses/mit-license>`_
Documentation Tool
sphynx
Application Documentation
`pydoc3.7 <https://gitlab.e-cam2020.eu/carrivain/plectonemes-with-openmm/blob/master/openmm_plectoneme_functions.html>`_
Relevant Training Material
`pdf documentation <https://gitlab.e-cam2020.eu/carrivain/plectonemes-with-openmm/blob/master/openmm_plectoneme.pdf>`_
Software Module Developed by
Pascal Carrivain
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.. _openmm_plectoneme:
##############################
E-CAM openmm_plectoneme module
##############################
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.. contents:: :local:
.. Add an abstract for a *general* audience here. Write a few lines that explains the "helicopter view" of why you are
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into YYYY process, which in turn should allow ZZZZ to be simulated. If successful, this could make it possible to
produce compound AAAA while avoiding expensive process BBBB and CCCC."
The openmm_plectoneme is a module that introduce twist to a ring or linear polymer and sample the accessible conformations under
torsional constraints. This module takes advantage of the OpenMM software and GPU acceleration to perform simulation at the scale
of the DNA helix. It builds a Kremer-Grest polymer model with virtual sites to attach a frame to each of the bead.
The frames are used to describe the contour of the molecule and to introduce bending and twisting forces.
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.. * Style *(use meaningful variable names, no global variables,...)*
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.. * Tests *(everything you add should have either unit or regression tests)*
.. * Performance *(If what you introduce has a significant computational load you should make some performance optimization
effort using an appropriate tool. You should be able to verify that your changes have not introduced unexpected
performance penalties, are threadsafe if needed,...)*
Purpose of Module
_________________
Bacterial DNA is known to form specific conformations called *plectonemes* because of internal twisting constraints.
This physical mechanism participates to the compaction of the genome.
The *plectonemes* are braided structures you often experiment with phone cables.
In order to study such a system we need to introduce a `linking number <https://en.wikipedia.org/wiki/Linking_number>`_ deficit into a circular polymer.
The Linking number (Lk) is the sum of the Twist (Tw, cumulative helicity of the DNA) and the Writhe (Wr, global intracity).
In the case of circular DNA that is topologically constrained any variation of the Twist affects the Writhe and therefore the conformation.
In particular, does slow change of the twist lead to the same conformation that the one we get from a rapidly change in the Twist ?
We then tackle the question : does the introduction protocol of Linking number inside circular molecule matter ?
Indeed, does a rapidly Linking number injection freeze the conformation in braided structures where *plectonemes* do not merge/move along the DNA ?
Does the memory of initial conformation matter ?
We can use this module to model single-molecule DNA under `magnetic or optical tweezers <https://en.wikipedia.org/wiki/Magnetic_tweezers>`_ too.
In this kind of setup the molecule is clamped on a plate and to a magnetic bead at the other extremity.
The bead is used to apply stretching force and/or rotational constraint.
The position of the bead is used to monitor the response of the molecule to the mechanical constraints.
From the mechanical constraints you can extract the mechanical properties of your molecule of interest.
This module assist the creation of polymer described by FENE bond and WCA repulsive potential to resolve the excluded volume constraints.
On top of that, the module introduces the twist and mechanical response to twisting constraint with the help of *virtual sites* functionalities from OpenMM API.
The module proposes functions to help the data analysis with High-Performance-Computing Dask software and Python module Numba.
For example, the estimation of the Writhe that is a computation over all the possible pairwize of bonds is highly expensive and can be fasten.
In addition to that, we introduce an algorithm to detect the positions, length and shape of *plectonemes*.
It is useful to follow the dynamics of these braided structures and try to answer the previous questions.
This module can be used by polymer physicist to understand the conformation of bacterial DNA under torsional constraints for example.
Indeed, it used in a scientific collaboration with Ivan Junier from TIMC-IMAG, Grenoble, France and Ralf Everaers, ENS Lyon, France.
However, the publication is not currently available.
Background Information
______________________
We use the OpenMM toolkit for molecular dynamics.
We implemented functionalities to build a frame (that follows the contour of the polymer) and add twisting energy to a Kremer-Grest polymer system.
We implemented function to extract *plectonemes*, `writhe <https://en.wikipedia.org/wiki/Writhe>`_ and `twist <https://en.wikipedia.org/wiki/Twist_(mathematics)>`_ from polymer conformations.
Building and Testing
____________________
The module openmm_plectoneme comes with an example script as well as a test script (using unittest python module).
In order to test the twist implementation we provide a script that make comparison between the twisting correlations
we measure from our model with the theoretical one.
We are currently working on a benchmark between the present module and already published `Monte-Carlo <https://www.sciencedirect.com/science/article/pii/S0378437119307204>`_
and `rigid body dynamics <https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1003456>`_ codes.
Source Code
___________
The source code and more information can be find on the `openmm_plectoneme GitLab repository <https://gitlab.e-cam2020.eu/carrivain/plectonemes-with-openmm>`_.