This title appears in the Scientific Report : 2020 

Stochastic thermodynamics and modes of operation of a ribosome: A network theoretic perspective
Dutta, Annwesha
Schütz, Gunter M. / Chowdhury, Debashish (Corresponding author)
Theoretische Physik der Lebenden Materie; IBI-5
Physical review / E covering statistical, nonlinear, biological, and soft matter physics, 101 (2020) 3, S. 032402
Woodbury, NY Inst. 2020
Journal Article
Functional Macromolecules and Complexes
Please use the identifier: in citations.
Please use the identifier: in citations.
The ribosome is one of the largest and most complex macromolecular machines in living cells. It polymerizes a protein in a step-by-step manner as directed by the corresponding nucleotide sequence on the template messenger RNA (mRNA) and this process is referred to as “translation” of the genetic message encoded in the sequence of mRNA transcript. In each successful chemomechanical cycle during the (protein) elongation stage, the ribosome elongates the protein by a single subunit, called amino acid, and steps forward on the template mRNA by three nucleotides called a codon. Therefore, a ribosome is also regarded as a molecular motor for which the mRNA serves as the track, its step size is that of a codon and two molecules of GTP and one molecule of ATP hydrolyzed in that cycle serve as its fuel. What adds further complexity is the existence of competing pathways leading to distinct cycles, branched pathways in each cycle, and futile consumption of fuel that leads neither to elongation of the nascent protein nor forward stepping of the ribosome on its track. We investigate a model formulated in terms of the network of discrete chemomechanical states of a ribosome during the elongation stage of translation. The model is analyzed using a combination of stochastic thermodynamic and kinetic analysis based on a graph-theoretic approach. We derive the exact solution of the corresponding master equations. We represent the steady state in terms of the cycles of the underlying network and discuss the energy transduction processes. We identify the various possible modes of operation of a ribosome in terms of its average velocity and mean rate of GTP hydrolysis. We also compute entropy production as functions of the rates of the interstate transitions and the thermodynamic cost for accuracy of the translation process.