||Translation is modeled as a hierarchical process similar to transcription. At the top level each ribosome can exist in four states – free 30S and 50S ribosomal particles and initiation factor 3 (IF-3), an assembled 70S ribosomal particle - IF-3 complex, an actively translating 70S ribosomal particle, and a stalled 70S ribosomal particle. First, 70S ribosomal particle - IF-3 complexes are assembled according to available subunits. Second, newly assembled complexes stochastically bind mRNAs according to their abundance. Permitting the availability of initiation factors 1 and 2, ribosomes progress to the actively translating state, and initiation factor 1 is released to the free pool. Next, the available elongation factors and aminoacylated tRNAs are allocated among the actively translating ribosomes. Finally, subject to the availability of termination and recycling factors, completed polypeptides are released, and the corresponding ribosomes are disassembled and released to the free state.
Evolves the states of ribosomes among two states
Transition to from the free state to the actively translating state is allowed when
ribosome binding factor A is present
initiation factors (IF-1, IF-2, and IF-3) are present
one unit of energy (GTP) is available.
At this time the ribosome binds an mRNA randomly with uniform probability.
At the next iteration the initiation factors are released when the first amino acid, f-methionine binds and elongation begins, assuming that elongation factors (EF-tu, TS, and G) and energy (GTP) is availble.
ASSUMPTION made here is that one of each is sufficient for each ribosome, but need a separate set for each ribosome. So each ribosome can only translate if a full set exists for it. Also, for cases in which translation of a peptide finishes partway through the time step, the EFs are free, but haven't added the complexity of another ribosome being able to take up EFs partway through the timestep.
Finally, once all amino acids of a protein have been translated, termination occurs if
at least one terminator (RF-1) available
at least one recycling factor available
at least one elongation factor G available
at least one trigger factor available
energy is available.
The ribosome will be available to bind mRNA at the following iteration.
Ribosomes are created in the free state.
The translation of stalled ribosomes is terminated by the protein SmpB and small non-coding RNA tmRNA. First, SmpB identifies a stalled ribosome. Second, SmpB recruits an alanine-conjugated tmRNA, and the tRNA domain of the tmRNA binds the ribosome A site. Third, the mRNA domain of the tmRNA expels and replaces the mRNA, becoming the template for a 26 amino acid long C-terminal proteolysis tag which targets the nascent peptide to the FtsH protease. Next, translation resumes and the proteolysis tag is synthesized. Upon release the nascent peptide is identified and cleaved by the FtsH protease as described below.
The stalled ribosome response is modeled as a stochastic, low probability event within the actively translating state of the translation module. First, if the translation of a peptide does not advance within a time step, then with small probability, and subject to the availability of SmpB and tmRNA, the ribosome transitions to the stalled state. Second, the stalled state is modeled identically to the actively translating state, except that the tmRNA is used as the mRNA template, and upon termination the peptide enters the proteolysis tagged pool to be degraded by the FtsH protease.
Amino acid misincorporation
Amino acid misincorporation was studied by Zaher and Green [PUB_0028]. Amino acid misincorporation is not currently modeled.