2023
DOI: 10.1038/s41467-023-36705-8
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Size limits the sensitivity of kinetic schemes

Abstract: Living things benefit from exquisite molecular sensitivity in many of their key processes, including DNA replication, transcription and translation, chemical sensing, and morphogenesis. At thermodynamic equilibrium, the basic biophysical mechanism for sensitivity is cooperative binding, for which it can be shown that the Hill coefficient, a sensitivity measure, cannot exceed the number of binding sites. Generalizing this fact, we find that for any kinetic scheme, at or away from thermodynamic equilibrium, a ve… Show more

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Cited by 17 publications
(6 citation statements)
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“…have degree 2 m − 1 in x [1] and can therefore have substantially higher sharpness than responses at t.e. [25]. It is this marked difference in rational structure that underlies Fig.3C and explains the failure of universality away from t.e.…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…have degree 2 m − 1 in x [1] and can therefore have substantially higher sharpness than responses at t.e. [25]. It is this marked difference in rational structure that underlies Fig.3C and explains the failure of universality away from t.e.…”
Section: Resultsmentioning
confidence: 99%
“…The use of graphs to study Markov processes has its roots in the pioneering work of Hill [20] and Schnakenberg [21]. It is rarely seen in the Markov process literature and has only occasionally appeared in the biophysics literature [22], until the development of the linear framework [23, 24, 25, 26]. The main distinction in the linear framework approach is to treat the graph as a mathematical object in its own right, in terms of which results can be formulated, which, as we will see here, can accommodate some of the molecular complexity found in biology.…”
Section: Resultsmentioning
confidence: 99%
“…The use of graphs to study Markov processes has its roots in the pioneering work of Hill ( 20 ) and Schnakenberg ( 21 ). It is rarely seen in the Markov process literature and has only occasionally appeared in the biophysics literature ( 22 ), until the development of the linear framework ( 23 26 ). The main distinction in the linear framework approach is to treat the graph as a mathematical object in its own right, in terms of which results can be formulated, which, as we will see here, can accommodate some of the molecular complexity found in biology.…”
Section: Resultsmentioning
confidence: 99%
“…have degree in ( 1 ) and can therefore have substantially higher sharpness than responses at t.e. ( 25 ). It is this marked difference in rational structure that underlies Fig.…”
Section: Resultsmentioning
confidence: 99%
“…† Throughout our analysis and discussion in this paper, we monitor the shape, number of inflection points, and sensitivity of transcriptional outputs with respect to the control parameter of the concentration of transcription factor, on a logarithmic scale. We use this logarithmic convention in alignment with common practice in biochemical and transcriptional studies(6,28,29).…”
mentioning
confidence: 99%