359 research outputs found
Maximizing Protein Translation Rate in the Ribosome Flow Model: the Homogeneous Case
Gene translation is the process in which intracellular macro-molecules,
called ribosomes, decode genetic information in the mRNA chain into the
corresponding proteins. Gene translation includes several steps. During the
elongation step, ribosomes move along the mRNA in a sequential manner and link
amino-acids together in the corresponding order to produce the proteins.
The homogeneous ribosome flow model(HRFM) is a deterministic computational
model for translation-elongation under the assumption of constant elongation
rates along the mRNA chain. The HRFM is described by a set of n first-order
nonlinear ordinary differential equations, where n represents the number of
sites along the mRNA chain. The HRFM also includes two positive parameters:
ribosomal initiation rate and the (constant) elongation rate. In this paper, we
show that the steady-state translation rate in the HRFM is a concave function
of its parameters. This means that the problem of determining the parameter
values that maximize the translation rate is relatively simple. Our results may
contribute to a better understanding of the mechanisms and evolution of
translation-elongation. We demonstrate this by using the theoretical results to
estimate the initiation rate in M. musculus embryonic stem cell. The underlying
assumption is that evolution optimized the translation mechanism.
For the infinite-dimensional HRFM, we derive a closed-form solution to the
problem of determining the initiation and transition rates that maximize the
protein translation rate. We show that these expressions provide good
approximations for the optimal values in the n-dimensional HRFM already for
relatively small values of n. These results may have applications for synthetic
biology where an important problem is to re-engineer genomic systems in order
to maximize the protein production rate
Analyzing Linear Communication Networks using the Ribosome Flow Model
The Ribosome Flow Model (RFM) describes the unidirectional movement of
interacting particles along a one-dimensional chain of sites. As a site becomes
fuller, the effective entry rate into this site decreases. The RFM has been
used to model and analyze mRNA translation, a biological process in which
ribosomes (the particles) move along the mRNA molecule (the chain), and decode
the genetic information into proteins.
Here we propose the RFM as an analytical framework for modeling and analyzing
linear communication networks. In this context, the moving particles are
data-packets, the chain of sites is a one dimensional set of ordered buffers,
and the decreasing entry rate to a fuller buffer represents a kind of
decentralized backpressure flow control. For an RFM with homogeneous link
capacities, we provide closed-form expressions for important network metrics
including the throughput and end-to-end delay. We use these results to analyze
the hop length and the transmission probability (in a contention access mode)
that minimize the end-to-end delay in a multihop linear network, and provide
closed-form expressions for the optimal parameter values
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