Modeling dynamics of Translation: with mRNA sequences

Instructions
If you don't see a picture above with RNA and various regulatory buttons, please install newest version of Java.

mRNA selection (Initiation): One can choose out of 5 mRNA sequences, which are the sequence of three kinds of codon ratess A, B, and C. One can change them by changing number in "mRNA selection" box. (1: pMAS23, 2: 24GAA insert, 3:24GAG insert, 4:48GAA insert, 5: 48GAG insert. For detailed information about the mRNAs, see Sorensen and Pedersen 1991)

PARAMETERS
(Initiation):

Initiation occurs as follows;
(i) Binding rate of ribosome is given by "on rate" (1/s). The default setting is 1/1.1 (1/sec).
(ii) When a ribosome bind to the first codon, the ribosome takes 0.2 sec to start translation.
The clearance time depends on the first eleven codons. It is the sum of [1/(rate to move for each codon)] for the first eleven codons.

(Elongation):

Elongation occurs stochastically. A ribosome occupies 11 codons, and it proceeds with a rate given to each codons.
One can chose the rate for each kind of codons. The default setting is 35 [1/s] for A, 8 [1/s] for B, 4.5 [1/s] for C. The mRNA sequence gives which codon is A, B, or C. In the middle, the color shows the position of A codon by grey, B codon by yellow, and C codon by orange.

(Termination):

The termination can take long time. One can choose the average time for a ribosome to leave from the termination site in the box of "terminate"(sec). The default setting is 0.5 sec.

There is a button to "Start/stop degradation". When one starts the degradation, the degradation of mRNA happens stochastically with average 30 translation per mRNA. The default setting is no degradation.

The button "Stocastic/Deteministic" changes whether the ribosome dynamics is stocastic or deteministic. The default setting is stochastic dynamics.

The simulation speed can be controlled by the scroll bar.

Graphs

On the right top, one can see two types of graphs.

If one choose "spatiotemporal", one get spatiotemporal plots, where spatial axis along mRNA is in horizontal direction, and time axis in vertical direction. One can see the effect of queueing clearly.

The choice of "Experiment" is useful only if one press the button "Start Experiment". See below.

Experiment When one press "Start Experiment", the simulation of the experiment to measure the incorporation of radioactive methionine in Sorensen and Pedersen 1991 starts. In the experiment, a pulse of radioactive methionine is added for 10 seconds, and the incorporated radioactive signals in the finished peptides are measured in the course of time. In the applet, the methionine that a ribosome carrying is shown by black dots below each ribosome when there is no radioactive pulse. When the radioactive pulse is given, the bottom half of the background is shown as white, and the radioactive methionine that are incorporated during the pulse are shown by red dots below each ribosome. The graph at the right top shows the time course of measured radioactive signals in an arbitrary unit.

Philosophy

References:

Namiko Mitarai, Kim Sneepen, and Steen Pedersen, "Ribosome collisions and Translation efficiency: Optimization by codon usage and mRNA destabilization" J. Mol. Biol. 382, p.236 (2008)

J. E. Bergmann and H. F. Lodish, "A Kinetic Model of Protein Synthesis", J. Bio. Chem. 254, p.11927 (1979)

M. A. Sorensen and S. Pedersen, "Absolute in Vivo Translation Rates of Individual Codons in Escherichia coli' The Two Glutamic Acid Codons GAA and GAG Are Translated with a Threefold Difference in Rate" J. Mol. Biol. 222, p.265 (1991)