This project models ribosome motion during genetic translation using the Totally Asymmetric Simple Exclusion Process (TASEP) and validates the model with simulations. The framework is extended to a ballistic model, an approximation of TASEP in the low-density regime, characterized by deterministic ribosome movement without excluded volume interactions, while incorporating finite mRNA lifetime. The model partitions mRNAs into k-somes (monosomes, disomes, trisomes, and tetrasomes) and estimates kinetic parameters, namely the initiation rate 'α' and the elongation rate 'p', by fitting to Ribo-seq experimental data.
The Totally Asymmetric Simple Exclusion Process (TASEP) is a stochastic model describing particles moving unidirectionally along a one-dimensional lattice under an exclusion constraint, where each site can be occupied by at most one particle. This framework is applied to ribosome translation on mRNA.
In this model:
- Ribosomes initiate at the first site with rate
α, - Elongate along the lattice with rate
p, provided the next site is unoccupied, - Terminate at the final site with rate
β, - Taking into account the finite mRNA lifetime, degradation occurs with rate
ω.
The random sequential update rule is used:
- At each time step, a site is randomly selected.
- If the site is occupied and the next site is empty, the particle moves with probability ( p ).
- Particles enter and exit based on the boundary conditions ( \alpha ) and ( \beta ).
- Derrida, B., Domany, E., & Mukamel, D. (1992). Exact solution of a one-dimensional asymmetric exclusion model with open boundaries. Journal of Statistical Physics.
- MacDonald, C. T., Gibbs, J. H., & Pipkin, A. C. (1968). Kinetics of biopolymerization on nucleic acid templates. Biopolymers.
- Chevalier, C., Dorignac, J., Ibrahim, Y., Choquet, A., David, A., Ripoll, J., Rivals, E., Geniet, F., Walliser, N.-O., Palmeri, J., Parmeggiani, A., & Walter, J.-C. (2022). Physical modeling of ribosomes along messenger RNA: Estimating kinetic parameters from ribosome profiling experiments using a ballistic model. arXiv preprint arXiv:2208.12576. https://arxiv.org/abs/2208.12576