E-CAM openmm_copolymer module¶
openmm_copolymer is a module that samples conformation of a block-copolymer given an epigenome state file. This module takes advantage of the OpenMM API and GPU acceleration. It builds a Kremer-Grest polymer model with uni-dimensional epigenetic information and constructs the epigenetic interactions based on the model you design. You simply need to feed the module with an epigenome state file, the interaction model and the mechanical properties of the polymer.
You can use the module to model small part of an epigenome or the whole genome confined inside the cell nucleus.
The epigenetic and the tri-dimensional structure of fly genome is studied by means of a block-copolymer (polymer made of more than one monomer species). The epigenetic information does not involve alterations in the DNA but histone tails modifications. This uni-dimensional information can be projected along the contour of a block-copolymer model.
Then, there is pairwise interaction of monomers according to the epigenetic states, leading to specific pattern of interactions. The interaction patterns can be visualized using contacts map: two-dimensional map with positions along the polymer and a third dimension with color scale for the intensity of contacts.
Since 2000, biologists can produce this same kind of data thanks to the high-throughput-sequencing methods 3C, 4C, 5C and Hi-C: Chromosome-Conformation-Capture. Recently, biologists have shown that the interactions pattern is correlated with the epigenetic information. However, the strength and model of interactions between epigenetic states are not always clearly known.
In addition to the high-throughput-sequencing methods, we can study the spatial distances inside part of the genome with the help of FISH and high-resolution methods. All the spatial distances can be simply extracted from the model we built with the help of openmm_copolymer module.
The module we propose uses the OpenMM API with GPU acceleration to sample as many epigenetic parameters as possible.
It is possible to use effective interactions (gaussian overlap or Lennard-Jones potential) to model the epigenetics. The module introduces the possibility to replace effective epigenetic interactions with binders model too. In this case, the binder is like a protein that can bind to a specific site of the genome. A simple input file is enough to tell the script about the binder-binder and monomer-binder interactions.
The module includes pairing potential, nucleus confinement potential as-well-as genome examples.
It can be used by polymer physicists, biophysicists for epigenetic modeling, to understand the link between epigenetic and tri-dimensional structure of a genome, to estimate first-passage-time encounter of two locii. It is used in a scientific collaboration to study a specific promoter-enhancer system and homeotic gene complexes in the fruit-fly organism (ENS Lyon, France). However, the publication is not currently available.
We use the OpenMM API for molecular dynamics. We implemented functionalities to build a Kremer-Grest polymer system with uni-dimensional epigenetic information. We also implement functions to build the quantities biologists extract from high-throughput-sequencing and FISH experiments.
You can find pdf file with a detailed description on the openmm_copolymer GitLab repository. The module will be constantly improved with new functionalities.
The instructions to install, test and run the module can be find on the openmm_copolymer GitLab repository.