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SUMMARY:Substrate Enzyme-Sequestration in Multisite Protein Phosphorylatio
 n - Introducing WCDD M-matrices in designing stationary probability distri
 butions - Andreas Petrides\, University of Cambridge
DTSTART:20161124T140000Z
DTEND:20161124T150000Z
UID:TALK68250@talks.cam.ac.uk
CONTACT:Tim Hughes
DESCRIPTION:Multisite protein phosphorylation has been of great interest t
 o the systems biology community due to its ability to exhibit multistable 
 behaviour. In the presence of excess substrate\, ultrasensitivity can be o
 btained which\, when coupled with positive feedback\, can result in bistab
 ility. In this same regime\, Thomson and Gunawardena showed that the numbe
 r of stable steady states achieved can increase linearly with the number o
 f phosphosites available\, without the need of positive feedback. In the r
 egime of excess enzyme\, Martins and Swain showed that substrate enzyme se
 questration of the fully unphosphorylated and the fully phosphorylated sub
 strates can provide the necessary ultrasensitivity.\n\nWe first illustrate
  that substrate enzyme sequestration can limit the number of steady states
  calculated for a particular system with large numbers and excess substrat
 e (without positive feedback)\, giving a sufficient condition relating the
  sequestration parameters to the rest of the system's parameters.\nHowever
 \, we also show that substrate enzyme sequestration in the low substrate n
 umbers/excess enzyme regime can exhibit multimodality even when there is o
 nly one available phosphosite. In fact\, we illustrate that substrate enzy
 me-sequestration can turn monomodality to bimodality in the low substrate 
 number regime in the presence of a single available phosphosite.\nIn this 
 regime\, the analysis is naturally placed in the stochastic domain. Theref
 ore\, we also present a weakly chained diagonally dominant M-matrix formul
 ation of the Chemical Master Equation\, which has the ability to act both 
 as an accurate computational method and as a framework tool in designing s
 tationary probability distributions for systems where the Markov process c
 haracterisation is the most applicable.\nIt is suggested that substrate en
 zyme sequestration might be beneficial in obtaining multimodality in the l
 ow substrate numbers/excess enzyme regime\, at the expense of limiting the
  extent of multistability that can be achieved in the large numbers/excess
  substrate regime.
LOCATION:Cambridge University Engineering Department\, LR4
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