In this project we are attempting to create a molecularly accurate simulation of the process of DNA replication and separation during the process of cell division in prokaryotic bacteria cells. We are using a software devloped at Caltech known as moltemplate to initialize the simulations, and LAMMPS to run them. Understanding the foundational principles that govern the replication process is at the forefront of cutting edge Biophysics research and we are seeking to make BYU one of the foremost universities in the subject. Applications of these simulations are theoretically limitless, being able to adapt medicines and treatments to target the replication of DNA in harmful bacteria in our bodies could be a solution to bacterial infections as antibiotic resistance is on the rise. Many more applications are likely to be found as we begin to develop the world's understanding of the field.
Our current focus is understanding and creating accurate visualizations of the nucleoid associated proteins (NAPS) that assist in the compaction, replication, and transcription of DNA. See the 4CS folder for the work we completed and presented on at the 4 corners APS meeting 2022.
Moltemplate is a molecular dynamics software that creates input files that Lammps uses to run its simulations. Check out the Moltemplate directory for more info and for some tutorials to get familiar with running simulations with it.
Vmd is a visualization software we use to visualize the results of our simulations. You'll become familiar with using the VMD GUI by running through the moltemplate tutorials, but for info and tutorial examples on running VMD through scripts on the supercomputer, check out the tutorials in the VMD directory.
If you need help getting set up on the supercomputer, you can apply for an account here and see instructions on how to set up remote access through VS Code here. Check out this great seminar put on by BYUSupercomputing for a fairly comprehensive beginner's introduction to the supercomputer and how it all works.
These academic articles are very relevant base information to understand as we proceed with our tasks.
- This is a great paper which goes in depth into each of the nucleoid associated proteins that take part in DNA compaction and organization
- This paper expounds upon the newly discovered complexitiy within prokaryotic DNA formations
- This paper describes recent developments in the understanding of internal nucleoid structure as well as the dynamics of sister chromosome segregation
- This paper goes more in depth on the spatial order required to maintain functionality of DNA repication
- These papers explain how bacterial structure can vary based on growth/replication conditions in the growth phase
- This paper talks about the ever increasing use of math in Biology as well as the abuses and things to be wary of when using mathematical models to simulate biological functions. Very important to remember when doing simulations such as the ones we are doing.
First things first, it is crucial that we have a basic understanding of what current science knows about the replication and division process. Check out the following resources for some basic information.
- This section from a Biology Textbook on Prokaryotic DNA Replication
- These two videos show incredible and fascinating simulations that have already been created for DNA replication and other processes in the cell. Drew Barry Ted Talk and Animations Video.
DNA utilizes supercoiling to pack the immense length of its strands into a microscopic space, and the Topoisomerase lessens the strain as the DNA replicates.
- This video explains the idea of DNA supercoiling
- This video has a great explanation of the Topoisomerase Enzyme which is very important in our simulation of DNA Separation
The nucleoid structure employed by bacteria is suprisingly complex, and uses multiple layers as well as differening topological regions to organize the chromosome.
- This video is simple yet descriptive in showing the way the nucleoid is compacted
- This Wikipedia article explains the structure of the nucleoid and chromosomes in a prokaryotic cell and will be helpful in understanding the organization of DNA prior to replication.
- Another good video on Prokaryotic Nucleoids explains the way that DNA is organized.
git clone https://github.com/lammps/lammps.git
cd lammps/src
wget https://raw.githubusercontent.com/jewettaij/lammps/fix_twist/src/USER-MISC/fix_twist.cpp
wget https://raw.githubusercontent.com/jewettaij/lammps/fix_twist/src/USER-MISC/fix_twist.h
make yes-manybody
make yes-extra-pair
make yes-extra-molecule
make yes-molecule
module load intel-compilers/2019 intel-mpi/2019 libfabric/1.8
make -j mpi