We developed a module for the LAMMPS [0] to simulate loop extrusion. Loop extrusion is when active ATP-dependent motor (multiprotein complex) cohesin extrudes a loop from DNA [1]. We developed this module to study the effect of cohesin and CTCF on chromosome dynamics [2].
We simulate extruders (cohesins) as additional sliding links. With the predefined probability (P1) loop can be initiated between {i, i+2} beads and then every predefined number of steps (N1) we will try to shift it for 1 bead each base: [i, j] -> [i-1, j+1] -> [i-2, j+2] and so on. There is a predefined probability of releasing the extruder from the chain (P2). Extruders cannot pass through each other, stalling until one of them is released. We also have three barriers: left, right, and roadblocks. Left barrier blocks loop coming from the right, left barrier blocks loop coming from the left, and roadblock blocks both.
Installation on linux can be done usin cmake (tested with v.3.15.5). When you are in the folder with the repository, execute these commands in a command line.
mkdir build
cd build
cmake -C ../cmake/presets/minimal.cmake -D PKG_MISC=on -D PKG_USER-LE=on -D PKG_MPIIO=on -D PKG_MOLECULE=on -D PKG_MC=on ../cmake
make -j20
Now you should have the compiled executable file lmp. More detailed information about the installation can be found on the LAMMPS web-site.
fix loop all extrusion 17500 1 2 3 1.0 2 4
Here is standard LAMMPS syntax:
fix - keyword
loop - the name of the fix
all - group of particles to which we apply this fix
extrusion - specific name of the fix
17500 - N1, amount of steps we try to shift links
1 - the type of neutral type monomers from the chain
2 - left barrier
3 - right barrier
1.0 - the probability of going through the block
2 - the bond type of the extruder
4 - the type of roadblocks
To run the code, one needs proper loading and unloading of extruders. There are two more fixes:
fix loading all ex_load 7000 1 1 1.12 2 prob 0.001 684474 iparam 1 1 jparam 1 1
fix unloading all ex_unload 7000 2 0.5 prob 0.001 456456
Their syntax is similar to creating and breaking bonds from the MC package from the LAMMPS website.
https://docs.lammps.org/fix_bond_create.html
https://docs.lammps.org/fix_bond_break.html
[0]. Plimpton, Steve. "Fast parallel algorithms for short-range molecular dynamics." Journal of computational physics 117.1 (1995): 1-19.
[1]. Fudenberg, Geoffrey, et al. "Formation of chromosomal domains by loop extrusion." Cell reports 15.9 (2016): 2038-2049.
[2]. Mach, Pia, et al. "Live-cell imaging and physical modeling reveal control of chromosome folding dynamics by cohesin and CTCF." BioRxiv (2022).