<?xml version="1.0"?>
<!-- FILE : cui_2008.xml
CREATED : 30th April 2008
LAST MODIFIED : 30th April 2008
AUTHOR : Catherine Lloyd
Bioengineering Institute
The University of Auckland
MODEL STATUS : This model conforms to the CellML 1.1 Specification.
DESCRIPTION : This file contains a CellML description of Cui and Kaandorp's 2008 mathematical model of the transcriptional response of zinc homeostasis system in E. coli.
CHANGES:
--><model xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:cellml="http://www.cellml.org/cellml/1.0#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" cmeta:id="cui_2008" name="cui_2008">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>Transcriptional response of zinc homeostasis system in E. coli</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Auckland Bioengineering Institute, The University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
This CellML model runs in both OpenCell and COR to recreate the published results. The units have been checked and they are consistent. In this particular version of the model the zinc-buffering effects of TPEN are NOT considered.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
ABSTRACT: BACKGROUND: The zinc homeostasis system in Escherichia coli is one of the most intensively studied prokaryotic zinc homeostasis systems. Its underlying regulatory machine consists of repression on zinc influx through ZnuABC by Zur (Zn2+ uptake regulator) and activation on zinc efflux via ZntA by ZntR (a zinc-responsive regulator). Although these transcriptional regulations seem to be well characterized, and there is an abundance of detailed in vitro experimental data available, as yet there is no mathematical model to help interpret these data. To our knowledge, the work described here is the first attempt to use a mathematical model to simulate these regulatory relations and to help explain the in vitro experimental data. RESULTS: We develop a unified mathematical model consisting of 14 reactions to simulate the in vitro transcriptional response of the zinc homeostasis system in E. coli. Firstly, we simulate the in vitro Zur-DNA interaction by using two of these reactions, which are expressed as 4 ordinary differential equations (ODEs). By imposing the conservation restraints and solving the relevant steady state equations, we find that the simulated sigmoidal curve matches the corresponding experimental data. Secondly, by numerically solving the ODEs for simulating the Zur and ZntR run-off transcription experiments, and depicting the simulated concentrations of zntA and znuC transcripts as a function of free zinc concentration, we find that the simulated curves fit the corresponding in vitro experimental data. Moreover, we also perform simulations, after taking into consideration the competitive effects of ZntR with the zinc buffer, and depict the simulated concentration of zntA transcripts as a function of the total ZntR concentration, both in the presence and absence of Zn(II). The obtained simulation results are in general agreement with the corresponding experimental data. CONCLUSION: Simulation results show that our model can quantitatively reproduce the results of several of the in vitro experiments conducted by Outten CE and her colleagues. Our model provides a detailed insight into the dynamics of the regulatory system and also provides a general framework for simulating in vitro metal-binding and transcription experiments and interpreting the relevant experimental data.
</para>
<para>
In 1999-2001, Outten <emphasis>et al.</emphasis> published a series of papers presenting data from several <emphasis>in vitro</emphasis> transcription and metal-binding competition experiments in <emphasis>E. coli.</emphasis> These studies provide a detailed data set on which a mathematical model can be based. In the study described here, Cui and Kaandorp have developed such a mathematical model, and they use it to simulate the <emphasis>in vitro</emphasis> transcriptional response of zinc homeostasis system in <emphasis>E. coli.</emphasis> <ulink url="http://www.cellerator.org/">Cellerator</ulink>, an open source software, was used to automatically generate the equations, and the model was subsequently translated into CellML to facilitate future model exchange, reuse and implementation.
</para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>model diagram</title>
</objectinfo>
<imagedata fileref="cui_2008.png"/>
</imageobject>
</mediaobject>
<caption>A schematic diagram of the reactions described in the model of zinc homeostasis system in Escherichia coli. Extracellular zinc enters the cytoplasm through ZnuABC and ZupT, where its presence can cause Zur to bind to the znu operator and repress the transcription of the znuACB gene cluster. Excess intracellular zinc ions are exported by ZntA and ZitB, and cytosolic zinc can bind with protein ZntR to form a strong transcriptional activator of the zntA gene. Cytoplasmic zinc trafficking may involve chaperone-like proteins. Abbreviations: Zur* : active Zur; ZntR* : active ZntR; C? : (a possible zinc chaperone protein whose existence is still under debate).</caption>
</informalfigure>
<para>
The original paper reference is cited below:
</para>
<para>
Jiangjun Cui, Jaap A. Kaandorp and Catherine M. Lloyd 2008, <emphasis>BMC Systems Biology</emphasis>, 2:89. <ulink url="http://www.ncbi.nlm.nih.gov/pubmed/18950480">PubMed ID: 18950480</ulink>
</para>
</sect1>
</article>
</documentation>
<units name="minute">
<unit multiplier="60.0" units="second"/>
</units>
<units name="molar">
<unit units="mole"/>
<unit exponent="-1" units="litre"/>
</units>
<units name="per_molar">
<unit exponent="-1" units="molar"/>
</units>
<units name="nanomolar">
<unit prefix="nano" units="mole"/>
<unit exponent="-1" units="litre"/>
</units>
<units name="first_order_rate_constant">
<unit exponent="-1" units="second"/>
</units>
<units name="second_order_rate_constant">
<unit exponent="-1" units="nanomolar"/>
<unit exponent="-1" units="second"/>
</units>
<units name="third_order_rate_constant">
<unit exponent="-2" units="nanomolar"/>
<unit exponent="-1" units="second"/>
</units>
<component name="environment">
<variable cmeta:id="environment_time" name="time" public_interface="out" units="second"/>
</component>
<!-- The 7 ODEs describing the Zur transcription assay -->
<component cmeta:id="Py" name="Py">
<variable cmeta:id="Py_Py" initial_value="25.0" name="Py" public_interface="out" units="nanomolar"/>
<variable name="Zn" public_interface="in" units="nanomolar"/>
<variable name="Py1" public_interface="in" units="nanomolar"/>
<variable name="r3" public_interface="in" units="third_order_rate_constant"/>
<variable name="r4" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci> Py </ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci> r4 </ci>
<ci> Py1 </ci>
</apply>
<apply>
<times/>
<ci> r3 </ci>
<apply>
<power/>
<ci> Zn </ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless"> 2 </cn>
</apply>
<ci> Py </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component cmeta:id="Py1" name="Py1">
<variable cmeta:id="Py1_Py1" initial_value="0.0" name="Py1" public_interface="out" units="nanomolar"/>
<variable name="Zn" public_interface="in" units="nanomolar"/>
<variable name="Py" public_interface="in" units="nanomolar"/>
<variable name="Dw" public_interface="in" units="nanomolar"/>
<variable name="Qw2" public_interface="in" units="nanomolar"/>
<variable name="r3" public_interface="in" units="third_order_rate_constant"/>
<variable name="r4" public_interface="in" units="first_order_rate_constant"/>
<variable name="k_1" public_interface="in" units="first_order_rate_constant"/>
<variable name="k1a" public_interface="in" units="second_order_rate_constant"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci> Py1 </ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci> r3 </ci>
<apply>
<power/>
<ci> Zn </ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless"> 2 </cn>
</apply>
<ci> Py </ci>
</apply>
<apply>
<times/>
<ci> k_1 </ci>
<ci> Qw2 </ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci> r4 </ci>
<ci> Py1 </ci>
</apply>
<apply>
<times/>
<ci> k1a </ci>
<ci> Dw </ci>
<ci> Py1 </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component cmeta:id="Dw" name="Dw">
<variable initial_value="4.0" name="Dw" public_interface="out" units="nanomolar"/>
<variable name="Qw2" public_interface="in" units="nanomolar"/>
<variable name="Py1" public_interface="in" units="nanomolar"/>
<variable name="Qw1" public_interface="in" units="nanomolar"/>
<variable name="Rw" public_interface="in" units="nanomolar"/>
<variable name="k1a" public_interface="in" units="second_order_rate_constant"/>
<variable name="k_1" public_interface="in" units="first_order_rate_constant"/>
<variable name="k2" public_interface="in" units="second_order_rate_constant"/>
<variable name="k_2" public_interface="in" units="first_order_rate_constant"/>
<variable name="k3" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci> Dw </ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci> k_1 </ci>
<ci> Qw2 </ci>
</apply>
<apply>
<times/>
<ci> k3 </ci>
<ci> Qw1 </ci>
</apply>
<apply>
<times/>
<ci> k_2 </ci>
<ci> Qw1 </ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci> k1a </ci>
<ci> Dw </ci>
<ci> Py1 </ci>
</apply>
<apply>
<times/>
<ci> k2 </ci>
<ci> Dw </ci>
<ci> Rw </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component cmeta:id="Rw" name="Rw">
<variable initial_value="50.0" name="Rw" public_interface="out" units="nanomolar"/>
<variable name="Dw" public_interface="in" units="nanomolar"/>
<variable name="Qw1" public_interface="in" units="nanomolar"/>
<variable name="k2" public_interface="in" units="second_order_rate_constant"/>
<variable name="k_2" public_interface="in" units="first_order_rate_constant"/>
<variable name="k3" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci> Rw </ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci> k3 </ci>
<ci> Qw1 </ci>
</apply>
<apply>
<times/>
<ci> k_2 </ci>
<ci> Qw1 </ci>
</apply>
</apply>
<apply>
<times/>
<ci> k2 </ci>
<ci> Dw </ci>
<ci> Rw </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component cmeta:id="Qw1" name="Qw1">
<variable initial_value="0.0" name="Qw1" public_interface="out" units="nanomolar"/>
<variable name="Dw" public_interface="in" units="nanomolar"/>
<variable name="Rw" public_interface="in" units="nanomolar"/>
<variable name="k2" public_interface="in" units="second_order_rate_constant"/>
<variable name="k_2" public_interface="in" units="first_order_rate_constant"/>
<variable name="k3" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci> Qw1 </ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci> k2 </ci>
<ci> Dw </ci>
<ci> Rw </ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci> k3 </ci>
<ci> Qw1 </ci>
</apply>
<apply>
<times/>
<ci> k_2 </ci>
<ci> Qw1 </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component cmeta:id="Qw2" name="Qw2">
<variable initial_value="0.0" name="Qw2" public_interface="out" units="nanomolar"/>
<variable name="Dw" public_interface="in" units="nanomolar"/>
<variable name="Py1" public_interface="in" units="nanomolar"/>
<variable name="k1a" public_interface="in" units="second_order_rate_constant"/>
<variable name="k_1" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci> Qw2 </ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci> k1a </ci>
<ci> Dw </ci>
<ci> Py1 </ci>
</apply>
<apply>
<times/>
<ci> k_1 </ci>
<ci> Qw2 </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component cmeta:id="Mw" name="Mw">
<variable initial_value="0.0" name="Mw" public_interface="out" units="nanomolar"/>
<variable name="Qw1" public_interface="in" units="nanomolar"/>
<variable name="k3" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci> Mw </ci>
</apply>
<apply>
<times/>
<ci> k3 </ci>
<ci> Qw1 </ci>
</apply>
</apply>
</math>
</component>
<!-- The 10 ODEs to describe the ZntR transcription assay -->
<component cmeta:id="Px" name="Px">
<variable cmeta:id="Px_Px" initial_value="25.0" name="Px" public_interface="out" units="nanomolar"/>
<variable name="Zn" public_interface="in" units="nanomolar"/>
<variable name="Px1" public_interface="in" units="nanomolar"/>
<variable name="Dz" public_interface="in" units="nanomolar"/>
<variable name="Qz4" public_interface="in" units="nanomolar"/>
<variable name="r1" public_interface="in" units="second_order_rate_constant"/>
<variable name="r2" public_interface="in" units="first_order_rate_constant"/>
<variable name="k1b" public_interface="in" units="second_order_rate_constant"/>
<variable name="k_1" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci> Px </ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci> r2 </ci>
<ci> Px1 </ci>
</apply>
<apply>
<times/>
<ci> k_1 </ci>
<ci> Qz4 </ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci> r1 </ci>
<ci> Zn </ci>
<ci> Px </ci>
</apply>
<apply>
<times/>
<ci> k1b </ci>
<ci> Dz </ci>
<ci> Px </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component cmeta:id="Px1" name="Px1">
<variable cmeta:id="Px1_Px1" initial_value="0.0" name="Px1" public_interface="out" units="nanomolar"/>
<variable name="Zn" public_interface="in" units="nanomolar"/>
<variable name="Px" public_interface="in" units="nanomolar"/>
<variable name="Dz" public_interface="in" units="nanomolar"/>
<variable name="Qz2" public_interface="in" units="nanomolar"/>
<variable name="r1" public_interface="in" units="second_order_rate_constant"/>
<variable name="r2" public_interface="in" units="first_order_rate_constant"/>
<variable name="k1" public_interface="in" units="second_order_rate_constant"/>
<variable name="k_1" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci> Px1 </ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci> r1 </ci>
<ci> Zn </ci>
<ci> Px </ci>
</apply>
<apply>
<times/>
<ci> k_1 </ci>
<ci> Qz2 </ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci> r2 </ci>
<ci> Px1 </ci>
</apply>
<apply>
<times/>
<ci> k1 </ci>
<ci> Dz </ci>
<ci> Px1 </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component cmeta:id="Dz" name="Dz">
<variable initial_value="4.0" name="Dz" public_interface="out" units="nanomolar"/>
<variable name="Qz2" public_interface="in" units="nanomolar"/>
<variable name="Px" public_interface="in" units="nanomolar"/>
<variable name="Qz1" public_interface="in" units="nanomolar"/>
<variable name="Px1" public_interface="in" units="nanomolar"/>
<variable name="Qz4" public_interface="in" units="nanomolar"/>
<variable name="Rz" public_interface="in" units="nanomolar"/>
<variable name="k1" public_interface="in" units="second_order_rate_constant"/>
<variable name="k1b" public_interface="in" units="second_order_rate_constant"/>
<variable name="k_1" public_interface="in" units="first_order_rate_constant"/>
<variable name="k2a" public_interface="in" units="second_order_rate_constant"/>
<variable name="k_2" public_interface="in" units="first_order_rate_constant"/>
<variable name="k3" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci> Dz </ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci> k_1 </ci>
<ci> Qz2 </ci>
</apply>
<apply>
<times/>
<ci> k3 </ci>
<ci> Qz1 </ci>
</apply>
<apply>
<times/>
<ci> k_2 </ci>
<ci> Qz1 </ci>
</apply>
<apply>
<times/>
<ci> k_1 </ci>
<ci> Qz4 </ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci> k1b </ci>
<ci> Dz </ci>
<ci> Px </ci>
</apply>
<apply>
<times/>
<ci> k1 </ci>
<ci> Dz </ci>
<ci> Px1 </ci>
</apply>
<apply>
<times/>
<ci> k2a </ci>
<ci> Dz </ci>
<ci> Rz </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component cmeta:id="Rz" name="Rz">
<variable initial_value="50.0" name="Rz" public_interface="out" units="nanomolar"/>
<variable name="Qz1" public_interface="in" units="nanomolar"/>
<variable name="Dz" public_interface="in" units="nanomolar"/>
<variable name="Qz3" public_interface="in" units="nanomolar"/>
<variable name="Qz4" public_interface="in" units="nanomolar"/>
<variable name="Qz5" public_interface="in" units="nanomolar"/>
<variable name="Qz2" public_interface="in" units="nanomolar"/>
<variable name="k2b" public_interface="in" units="second_order_rate_constant"/>
<variable name="k2c" public_interface="in" units="second_order_rate_constant"/>
<variable name="k2a" public_interface="in" units="second_order_rate_constant"/>
<variable name="k_2" public_interface="in" units="first_order_rate_constant"/>
<variable name="k3" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci> Rz </ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci> k3 </ci>
<ci> Qz1 </ci>
</apply>
<apply>
<times/>
<ci> k_2 </ci>
<ci> Qz1 </ci>
</apply>
<apply>
<times/>
<ci> k3 </ci>
<ci> Qz3 </ci>
</apply>
<apply>
<times/>
<ci> k_2 </ci>
<ci> Qz3 </ci>
</apply>
<apply>
<times/>
<ci> k3 </ci>
<ci> Qz5 </ci>
</apply>
<apply>
<times/>
<ci> k_2 </ci>
<ci> Qz5 </ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci> k2a </ci>
<ci> Dz </ci>
<ci> Rz </ci>
</apply>
<apply>
<times/>
<ci> k2b </ci>
<ci> Qz4 </ci>
<ci> Rz </ci>
</apply>
<apply>
<times/>
<ci> k2c </ci>
<ci> Qz2 </ci>
<ci> Rz </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component cmeta:id="Qz1" name="Qz1">
<variable initial_value="0.0" name="Qz1" public_interface="out" units="nanomolar"/>
<variable name="Dz" public_interface="in" units="nanomolar"/>
<variable name="Rz" public_interface="in" units="nanomolar"/>
<variable name="k2a" public_interface="in" units="second_order_rate_constant"/>
<variable name="k_2" public_interface="in" units="first_order_rate_constant"/>
<variable name="k3" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci> Qz1 </ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci> k2a </ci>
<ci> Dz </ci>
<ci> Rz </ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci> k3 </ci>
<ci> Qz1 </ci>
</apply>
<apply>
<times/>
<ci> k_2 </ci>
<ci> Qz1 </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component cmeta:id="Qz2" name="Qz2">
<variable initial_value="0.0" name="Qz2" public_interface="out" units="nanomolar"/>
<variable name="Dz" public_interface="in" units="nanomolar"/>
<variable name="Rz" public_interface="in" units="nanomolar"/>
<variable name="Qz3" public_interface="in" units="nanomolar"/>
<variable name="Px1" public_interface="in" units="nanomolar"/>
<variable name="k1" public_interface="in" units="second_order_rate_constant"/>
<variable name="k_1" public_interface="in" units="first_order_rate_constant"/>
<variable name="k2c" public_interface="in" units="second_order_rate_constant"/>
<variable name="k3" public_interface="in" units="first_order_rate_constant"/>
<variable name="k_2" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci> Qz2 </ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci> k1 </ci>
<ci> Dz </ci>
<ci> Px1 </ci>
</apply>
<apply>
<times/>
<ci> k3 </ci>
<ci> Qz3 </ci>
</apply>
<apply>
<times/>
<ci> k_2 </ci>
<ci> Qz3 </ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci> k_1 </ci>
<ci> Qz2 </ci>
</apply>
<apply>
<times/>
<ci> k2c </ci>
<ci> Qz2 </ci>
<ci> Rz </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component cmeta:id="Qz3" name="Qz3">
<variable initial_value="0.0" name="Qz3" public_interface="out" units="nanomolar"/>
<variable name="Qz2" public_interface="in" units="nanomolar"/>
<variable name="Rz" public_interface="in" units="nanomolar"/>
<variable name="k2c" public_interface="in" units="second_order_rate_constant"/>
<variable name="k_2" public_interface="in" units="first_order_rate_constant"/>
<variable name="k3" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci> Qz3 </ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci> k2c </ci>
<ci> Qz2 </ci>
<ci> Rz </ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci> k3 </ci>
<ci> Qz3 </ci>
</apply>
<apply>
<times/>
<ci> k_2 </ci>
<ci> Qz3 </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component cmeta:id="Qz4" name="Qz4">
<variable initial_value="0.0" name="Qz4" public_interface="out" units="nanomolar"/>
<variable name="Dz" public_interface="in" units="nanomolar"/>
<variable name="Rz" public_interface="in" units="nanomolar"/>
<variable name="Qz5" public_interface="in" units="nanomolar"/>
<variable name="Px" public_interface="in" units="nanomolar"/>
<variable name="k1b" public_interface="in" units="second_order_rate_constant"/>
<variable name="k_1" public_interface="in" units="first_order_rate_constant"/>
<variable name="k2b" public_interface="in" units="second_order_rate_constant"/>
<variable name="k3" public_interface="in" units="first_order_rate_constant"/>
<variable name="k_2" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci> Qz4 </ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci> k1b </ci>
<ci> Dz </ci>
<ci> Px </ci>
</apply>
<apply>
<times/>
<ci> k3 </ci>
<ci> Qz5 </ci>
</apply>
<apply>
<times/>
<ci> k_2 </ci>
<ci> Qz5 </ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci> k_1 </ci>
<ci> Qz4 </ci>
</apply>
<apply>
<times/>
<ci> k2b </ci>
<ci> Qz4 </ci>
<ci> Rz </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component cmeta:id="Qz5" name="Qz5">
<variable initial_value="0.0" name="Qz5" public_interface="out" units="nanomolar"/>
<variable name="Qz4" public_interface="in" units="nanomolar"/>
<variable name="Rz" public_interface="in" units="nanomolar"/>
<variable name="k2b" public_interface="in" units="second_order_rate_constant"/>
<variable name="k_2" public_interface="in" units="first_order_rate_constant"/>
<variable name="k3" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci> Qz5 </ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci> k2b </ci>
<ci> Qz4 </ci>
<ci> Rz </ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci> k3 </ci>
<ci> Qz5 </ci>
</apply>
<apply>
<times/>
<ci> k_2 </ci>
<ci> Qz5 </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component cmeta:id="Mz" name="Mz">
<variable initial_value="0.0" name="Mz" public_interface="out" units="nanomolar"/>
<variable name="Qz1" public_interface="in" units="nanomolar"/>
<variable name="Qz3" public_interface="in" units="nanomolar"/>
<variable name="Qz5" public_interface="in" units="nanomolar"/>
<variable name="k3" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci> Mz </ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci> k3 </ci>
<ci> Qz1 </ci>
</apply>
<apply>
<times/>
<ci> k3 </ci>
<ci> Qz3 </ci>
</apply>
<apply>
<times/>
<ci> k3 </ci>
<ci> Qz5 </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="model_parameters">
<variable initial_value="2.73E2" name="r1" public_interface="out" units="second_order_rate_constant"/>
<variable initial_value="3.437E-4" name="r2" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="4.41E10" name="r3" public_interface="out" units="third_order_rate_constant"/>
<variable initial_value="9E-3" name="r4" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="1E-5" name="Zn" public_interface="out" units="nanomolar"/>
<variable initial_value="0.025" name="k1" public_interface="out" units="second_order_rate_constant"/>
<variable initial_value="1.0" name="k1a" public_interface="out" units="second_order_rate_constant"/>
<variable initial_value="1.253E-2" name="k1b" public_interface="out" units="second_order_rate_constant"/>
<variable initial_value="0.9" name="k_1" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0.02" name="k2" public_interface="out" units="second_order_rate_constant"/>
<variable initial_value="0.00005" name="k2a" public_interface="out" units="second_order_rate_constant"/>
<variable initial_value="0.0002" name="k2b" public_interface="out" units="second_order_rate_constant"/>
<variable initial_value="0.0037" name="k2c" public_interface="out" units="second_order_rate_constant"/>
<variable initial_value="0.3" name="k_2" public_interface="out" units="first_order_rate_constant"/>
<variable name="k3" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="1800.0" name="td0" units="second"/>
<variable initial_value="2700" name="td" units="second"/>
<variable name="time" public_interface="in" units="second"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> k3 </ci>
<piecewise>
<piece>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="first_order_rate_constant"> 0.0 </cn>
<apply>
<and/>
<apply>
<geq/>
<ci> time </ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="second"> 0.0 </cn>
</apply>
<apply>
<lt/>
<ci> time </ci>
<ci> td0 </ci>
</apply>
</apply>
</piece>
<piece>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="first_order_rate_constant"> 0.011 </cn>
<apply>
<and/>
<apply>
<geq/>
<ci> time </ci>
<ci> td0 </ci>
</apply>
<apply>
<lt/>
<ci> time </ci>
<ci> td </ci>
</apply>
</apply>
</piece>
</piecewise>
</apply>
</math>
</component>
<connection>
<map_components component_1="Py" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Py1" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Dw" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Rw" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Qw1" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Qw2" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Mw" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Px" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Px1" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Dz" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Rz" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Qz1" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Qz2" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Qz3" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Qz4" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Qz5" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Mz" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="model_parameters" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Py1" component_2="Py"/>
<map_variables variable_1="Py" variable_2="Py"/>
<map_variables variable_1="Py1" variable_2="Py1"/>
</connection>
<connection>
<map_components component_1="model_parameters" component_2="Py"/>
<map_variables variable_1="Zn" variable_2="Zn"/>
<map_variables variable_1="r3" variable_2="r3"/>
<map_variables variable_1="r4" variable_2="r4"/>
</connection>
<connection>
<map_components component_1="Dw" component_2="Py1"/>
<map_variables variable_1="Dw" variable_2="Dw"/>
<map_variables variable_1="Py1" variable_2="Py1"/>
</connection>
<connection>
<map_components component_1="Qw2" component_2="Py1"/>
<map_variables variable_1="Qw2" variable_2="Qw2"/>
<map_variables variable_1="Py1" variable_2="Py1"/>
</connection>
<connection>
<map_components component_1="model_parameters" component_2="Py1"/>
<map_variables variable_1="Zn" variable_2="Zn"/>
<map_variables variable_1="r3" variable_2="r3"/>
<map_variables variable_1="r4" variable_2="r4"/>
<map_variables variable_1="k_1" variable_2="k_1"/>
<map_variables variable_1="k1a" variable_2="k1a"/>
</connection>
<connection>
<map_components component_1="Qw1" component_2="Dw"/>
<map_variables variable_1="Qw1" variable_2="Qw1"/>
<map_variables variable_1="Dw" variable_2="Dw"/>
</connection>
<connection>
<map_components component_1="Qw2" component_2="Dw"/>
<map_variables variable_1="Qw2" variable_2="Qw2"/>
<map_variables variable_1="Dw" variable_2="Dw"/>
</connection>
<connection>
<map_components component_1="Rw" component_2="Dw"/>
<map_variables variable_1="Rw" variable_2="Rw"/>
<map_variables variable_1="Dw" variable_2="Dw"/>
</connection>
<connection>
<map_components component_1="model_parameters" component_2="Dw"/>
<map_variables variable_1="k2" variable_2="k2"/>
<map_variables variable_1="k_2" variable_2="k_2"/>
<map_variables variable_1="k3" variable_2="k3"/>
<map_variables variable_1="k_1" variable_2="k_1"/>
<map_variables variable_1="k1a" variable_2="k1a"/>
</connection>
<connection>
<map_components component_1="Qw1" component_2="Rw"/>
<map_variables variable_1="Qw1" variable_2="Qw1"/>
<map_variables variable_1="Rw" variable_2="Rw"/>
</connection>
<connection>
<map_components component_1="model_parameters" component_2="Rw"/>
<map_variables variable_1="k2" variable_2="k2"/>
<map_variables variable_1="k_2" variable_2="k_2"/>
<map_variables variable_1="k3" variable_2="k3"/>
</connection>
<connection>
<map_components component_1="model_parameters" component_2="Qw1"/>
<map_variables variable_1="k2" variable_2="k2"/>
<map_variables variable_1="k_2" variable_2="k_2"/>
<map_variables variable_1="k3" variable_2="k3"/>
</connection>
<connection>
<map_components component_1="model_parameters" component_2="Qw2"/>
<map_variables variable_1="k_1" variable_2="k_1"/>
<map_variables variable_1="k1a" variable_2="k1a"/>
</connection>
<connection>
<map_components component_1="Qw1" component_2="Mw"/>
<map_variables variable_1="Qw1" variable_2="Qw1"/>
</connection>
<connection>
<map_components component_1="model_parameters" component_2="Mw"/>
<map_variables variable_1="k3" variable_2="k3"/>
</connection>
<connection>
<map_components component_1="Px1" component_2="Px"/>
<map_variables variable_1="Px" variable_2="Px"/>
<map_variables variable_1="Px1" variable_2="Px1"/>
</connection>
<connection>
<map_components component_1="Dz" component_2="Px"/>
<map_variables variable_1="Px" variable_2="Px"/>
<map_variables variable_1="Dz" variable_2="Dz"/>
</connection>
<connection>
<map_components component_1="Qz4" component_2="Px"/>
<map_variables variable_1="Px" variable_2="Px"/>
<map_variables variable_1="Qz4" variable_2="Qz4"/>
</connection>
<connection>
<map_components component_1="model_parameters" component_2="Px"/>
<map_variables variable_1="Zn" variable_2="Zn"/>
<map_variables variable_1="r1" variable_2="r1"/>
<map_variables variable_1="r2" variable_2="r2"/>
<map_variables variable_1="k_1" variable_2="k_1"/>
<map_variables variable_1="k1b" variable_2="k1b"/>
</connection>
<connection>
<map_components component_1="Dz" component_2="Px1"/>
<map_variables variable_1="Px1" variable_2="Px1"/>
<map_variables variable_1="Dz" variable_2="Dz"/>
</connection>
<connection>
<map_components component_1="Qz2" component_2="Px1"/>
<map_variables variable_1="Px1" variable_2="Px1"/>
<map_variables variable_1="Qz2" variable_2="Qz2"/>
</connection>
<connection>
<map_components component_1="model_parameters" component_2="Px1"/>
<map_variables variable_1="Zn" variable_2="Zn"/>
<map_variables variable_1="r1" variable_2="r1"/>
<map_variables variable_1="r2" variable_2="r2"/>
<map_variables variable_1="k_1" variable_2="k_1"/>
<map_variables variable_1="k1" variable_2="k1"/>
</connection>
<connection>
<map_components component_1="Qz2" component_2="Dz"/>
<map_variables variable_1="Qz2" variable_2="Qz2"/>
<map_variables variable_1="Dz" variable_2="Dz"/>
</connection>
<connection>
<map_components component_1="Qz1" component_2="Dz"/>
<map_variables variable_1="Qz1" variable_2="Qz1"/>
<map_variables variable_1="Dz" variable_2="Dz"/>
</connection>
<connection>
<map_components component_1="Qz4" component_2="Dz"/>
<map_variables variable_1="Qz4" variable_2="Qz4"/>
<map_variables variable_1="Dz" variable_2="Dz"/>
</connection>
<connection>
<map_components component_1="Rz" component_2="Dz"/>
<map_variables variable_1="Rz" variable_2="Rz"/>
<map_variables variable_1="Dz" variable_2="Dz"/>
</connection>
<connection>
<map_components component_1="model_parameters" component_2="Dz"/>
<map_variables variable_1="k1" variable_2="k1"/>
<map_variables variable_1="k1b" variable_2="k1b"/>
<map_variables variable_1="k_1" variable_2="k_1"/>
<map_variables variable_1="k2a" variable_2="k2a"/>
<map_variables variable_1="k_2" variable_2="k_2"/>
<map_variables variable_1="k3" variable_2="k3"/>
</connection>
<connection>
<map_components component_1="Qz2" component_2="Rz"/>
<map_variables variable_1="Qz2" variable_2="Qz2"/>
<map_variables variable_1="Rz" variable_2="Rz"/>
</connection>
<connection>
<map_components component_1="Qz1" component_2="Rz"/>
<map_variables variable_1="Qz1" variable_2="Qz1"/>
<map_variables variable_1="Rz" variable_2="Rz"/>
</connection>
<connection>
<map_components component_1="Qz4" component_2="Rz"/>
<map_variables variable_1="Qz4" variable_2="Qz4"/>
<map_variables variable_1="Rz" variable_2="Rz"/>
</connection>
<connection>
<map_components component_1="Qz3" component_2="Rz"/>
<map_variables variable_1="Qz3" variable_2="Qz3"/>
<map_variables variable_1="Rz" variable_2="Rz"/>
</connection>
<connection>
<map_components component_1="Qz5" component_2="Rz"/>
<map_variables variable_1="Qz5" variable_2="Qz5"/>
<map_variables variable_1="Rz" variable_2="Rz"/>
</connection>
<connection>
<map_components component_1="model_parameters" component_2="Rz"/>
<map_variables variable_1="k2a" variable_2="k2a"/>
<map_variables variable_1="k2b" variable_2="k2b"/>
<map_variables variable_1="k2c" variable_2="k2c"/>
<map_variables variable_1="k_2" variable_2="k_2"/>
<map_variables variable_1="k3" variable_2="k3"/>
</connection>
<connection>
<map_components component_1="model_parameters" component_2="Qz1"/>
<map_variables variable_1="k2a" variable_2="k2a"/>
<map_variables variable_1="k_2" variable_2="k_2"/>
<map_variables variable_1="k3" variable_2="k3"/>
</connection>
<connection>
<map_components component_1="Qz3" component_2="Qz2"/>
<map_variables variable_1="Qz3" variable_2="Qz3"/>
<map_variables variable_1="Qz2" variable_2="Qz2"/>
</connection>
<connection>
<map_components component_1="model_parameters" component_2="Qz2"/>
<map_variables variable_1="k1" variable_2="k1"/>
<map_variables variable_1="k_1" variable_2="k_1"/>
<map_variables variable_1="k2c" variable_2="k2c"/>
<map_variables variable_1="k_2" variable_2="k_2"/>
<map_variables variable_1="k3" variable_2="k3"/>
</connection>
<connection>
<map_components component_1="model_parameters" component_2="Qz3"/>
<map_variables variable_1="k2c" variable_2="k2c"/>
<map_variables variable_1="k_2" variable_2="k_2"/>
<map_variables variable_1="k3" variable_2="k3"/>
</connection>
<connection>
<map_components component_1="Qz5" component_2="Qz4"/>
<map_variables variable_1="Qz5" variable_2="Qz5"/>
<map_variables variable_1="Qz4" variable_2="Qz4"/>
</connection>
<connection>
<map_components component_1="model_parameters" component_2="Qz4"/>
<map_variables variable_1="k1b" variable_2="k1b"/>
<map_variables variable_1="k_1" variable_2="k_1"/>
<map_variables variable_1="k2b" variable_2="k2b"/>
<map_variables variable_1="k_2" variable_2="k_2"/>
<map_variables variable_1="k3" variable_2="k3"/>
</connection>
<connection>
<map_components component_1="model_parameters" component_2="Qz5"/>
<map_variables variable_1="k2b" variable_2="k2b"/>
<map_variables variable_1="k_2" variable_2="k_2"/>
<map_variables variable_1="k3" variable_2="k3"/>
</connection>
<connection>
<map_components component_1="Qz1" component_2="Mz"/>
<map_variables variable_1="Qz1" variable_2="Qz1"/>
</connection>
<connection>
<map_components component_1="Qz3" component_2="Mz"/>
<map_variables variable_1="Qz3" variable_2="Qz3"/>
</connection>
<connection>
<map_components component_1="Qz5" component_2="Mz"/>
<map_variables variable_1="Qz5" variable_2="Qz5"/>
</connection>
<connection>
<map_components component_1="model_parameters" component_2="Mz"/>
<map_variables variable_1="k3" variable_2="k3"/>
</connection>
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"><rdf:Description rdf:about="#Qz4"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Qz4</title><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">apo-ZntA-DNA complex</alternative></rdf:Description><rdf:Description rdf:about="rdf:#fc2f7f62-4eab-4c67-a73d-8e2d1c22f132"><rdf:value xml:lang="en">This CellML model runs in both PCEnv and COR to recreate the published results. The units have been checked and they are consistent. In this particular version of the model the zinc-buffering effects of TPEN are NOT considered.</rdf:value><creator xmlns="http://purl.org/dc/elements/1.1/"><rdf:Description rdf:about="rdf:#6706406e-9d56-41e1-9cbd-bdc0ad7bd0d0"/></creator></rdf:Description><rdf:Description rdf:about="rdf:#f14655d9-65d5-419b-9fa5-a0ffb9f592a4"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">BMC Systems Biology</title></rdf:Description><rdf:Description rdf:about="rdf:#3fd2ed4a-2d7e-4c83-a7e6-dc3fa380b55c"><Given xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Catherine</Given><Family xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Lloyd</Family><Other xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">May</Other></rdf:Description><rdf:Description rdf:about="#Mz"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Mz</title><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">mRNA of ZnuC</alternative></rdf:Description><rdf:Description rdf:about="#Qz5"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Qz5</title><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">transcription initiation complex formed by Qz4 and Rz</alternative></rdf:Description><rdf:Description rdf:about="rdf:#742a7f53-bb6e-4a72-b307-b5e2f4b8d1ae"><first_page xmlns="http://www.cellml.org/bqs/1.0#" xml:lang="en">89</first_page><last_page xmlns="http://www.cellml.org/bqs/1.0#" xml:lang="en"></last_page><volume xmlns="http://www.cellml.org/bqs/1.0#" xml:lang="en">2</volume><Pubmed_id xmlns="http://www.cellml.org/bqs/1.0#" xml:lang="en">18950480</Pubmed_id><Journal xmlns="http://www.cellml.org/bqs/1.0#"><rdf:Description rdf:about="rdf:#f14655d9-65d5-419b-9fa5-a0ffb9f592a4"/></Journal><issued xmlns="http://purl.org/dc/terms/"><rdf:Description rdf:about="rdf:#03f0f646-71aa-470c-be97-560513f58350"/></issued><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Simulating in vitro transcriptional response of zinc homeostasis system in Escherichia coli</title><creator xmlns="http://purl.org/dc/elements/1.1/"><rdf:Description rdf:about="rdf:#ab2dca7f-740c-43db-bc4e-ad1aee3d1122"/></creator></rdf:Description><rdf:Description rdf:about="#Dz"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Dz</title><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">DNA of ZntA</alternative></rdf:Description><rdf:Description rdf:about="rdf:#8b6e0f70-ccbf-4618-970f-a2f74209f8a7"><Orgname xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">The University of Auckland</Orgname><Orgunit xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Auckland Bioengineering Institute</Orgunit></rdf:Description><rdf:Description rdf:about="#Py"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Py</title><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">Zur dimer containing one zinc ion per monomer</alternative><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">Zn2Zur</alternative></rdf:Description><rdf:Description rdf:about="#Rz"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Rz</title><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">RNA polymerase for zntA transcription</alternative></rdf:Description><rdf:Description rdf:about="rdf:#6c081611-fca7-4139-a8d5-0c2794745eb9"><FN xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en"></FN></rdf:Description><rdf:Description rdf:about="rdf:#65680464-585c-4f10-8218-cbd0af9b1f15"><Given xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Catherine</Given><Family xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Lloyd</Family><Other xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">M</Other></rdf:Description><rdf:Description rdf:about="#Px"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Px</title><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">apo-ZntR</alternative></rdf:Description><rdf:Description rdf:about="rdf:#120cce91-6e87-4748-9d8e-5472bc7850b2"><Pubmed_id xmlns="http://www.cellml.org/bqs/1.0#" xml:lang="en"></Pubmed_id><JournalArticle xmlns="http://www.cellml.org/bqs/1.0#"><rdf:Description rdf:about="rdf:#742a7f53-bb6e-4a72-b307-b5e2f4b8d1ae"/></JournalArticle></rdf:Description><rdf:Description rdf:about="#Qz2"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Qz2</title><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">ZnZutA-DNA complex</alternative></rdf:Description><rdf:Description rdf:about="rdf:#650ea023-73db-4668-a4db-cb88774b57c6"><rdf:type><rdf:Description rdf:about="http://www.cellml.org/bqs/1.0#Person"/></rdf:type><N xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#2c7e35b0-a330-4757-a905-05b5f42f4657"/></N></rdf:Description><rdf:Description rdf:about="rdf:#4952fd0d-749d-4f5c-aeca-6c78f9ceee74"><rdf:value xml:lang="en"></rdf:value><creator xmlns="http://purl.org/dc/elements/1.1/"><rdf:Description rdf:about="rdf:#6c081611-fca7-4139-a8d5-0c2794745eb9"/></creator></rdf:Description><rdf:Description rdf:nodeID="n1"><subject_type xmlns="http://www.cellml.org/bqs/1.0#" xml:lang="en">keyword</subject_type><rdf:value><rdf:Description rdf:nodeID="n2"/></rdf:value></rdf:Description><rdf:Description rdf:about="rdf:#3d6a53cd-ac83-4b55-ad42-6be346efd7a7"><Given xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">James</Given><Family xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Lawson</Family><Other xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Richard</Other></rdf:Description><rdf:Description rdf:about="#Dw"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Dw</title><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">DNA of ZnuC</alternative></rdf:Description><rdf:Description rdf:about="rdf:#2c7e35b0-a330-4757-a905-05b5f42f4657"><Given xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Jaap</Given><Family xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Kaandorp</Family><Other xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">A</Other></rdf:Description><rdf:Description rdf:about="rdf:#6706406e-9d56-41e1-9cbd-bdc0ad7bd0d0"><FN xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Catherine Lloyd</FN></rdf:Description><rdf:Description rdf:about="rdf:#fe682b50-c2f1-408e-aa1d-af29c209b795"><rdf:type><rdf:Description rdf:about="http://www.cellml.org/bqs/1.0#Person"/></rdf:type><N xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#65680464-585c-4f10-8218-cbd0af9b1f15"/></N></rdf:Description><rdf:Description rdf:about="rdf:#8867d5ff-ca9d-4bd2-ab6a-c7ffee3a202f"><W3CDTF xmlns="http://purl.org/dc/terms/" xml:lang="en">2008-10-28T00:00:00+00:00</W3CDTF></rdf:Description><rdf:Description rdf:about="#Px1"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Px1</title><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">active ZntR</alternative><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">ZnZntR</alternative></rdf:Description><rdf:Description rdf:nodeID="n3"><maximumStepSize xmlns="http://www.cellml.org/metadata/simulation/1.0#" xml:lang="en">0.01</maximumStepSize><endingValue xmlns="http://www.cellml.org/metadata/simulation/1.0#" xml:lang="en">2</endingValue><pointDensity xmlns="http://www.cellml.org/metadata/simulation/1.0#nonstandard-" xml:lang="en">10000</pointDensity></rdf:Description><rdf:Description rdf:about="#Qz3"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Qz3</title><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">transcription initiation complex formed by Qz2 and Rz</alternative></rdf:Description><rdf:Description rdf:about="#Rw"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Rw</title><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">RNA polymerase for znuC transcription</alternative></rdf:Description><rdf:Description rdf:about="#cui_2008"><reference xmlns="http://www.cellml.org/bqs/1.0#"><rdf:Description rdf:about="rdf:#120cce91-6e87-4748-9d8e-5472bc7850b2"/></reference><reference xmlns="http://www.cellml.org/bqs/1.0#"><rdf:Description rdf:nodeID="n4"/></reference><simulation xmlns="http://www.cellml.org/metadata/simulation/1.0#"><rdf:Description rdf:nodeID="n5"/></simulation><cmeta:comment><rdf:Description rdf:about="rdf:#4952fd0d-749d-4f5c-aeca-6c78f9ceee74"/></cmeta:comment></rdf:Description><rdf:Description rdf:nodeID="n6"><rdf:first><rdf:Description rdf:nodeID="n3"/></rdf:first><rdf:rest><rdf:Description rdf:about="http://www.w3.org/1999/02/22-rdf-syntax-ns#nil"/></rdf:rest></rdf:Description><rdf:Description rdf:about="#Qw2"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Qw2</title><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">Zn4Zur-DNA complex</alternative></rdf:Description><rdf:Description rdf:about="rdf:#f13c6b6e-0e1a-4261-87b6-ab969e7ebe7f"><cmeta:modifier><rdf:Description rdf:about="rdf:#72f2ffc1-9066-4c1d-ad2f-b2e5baabdb5f"/></cmeta:modifier><modified xmlns="http://purl.org/dc/terms/"><rdf:Description rdf:about="rdf:#6af6c154-b9f3-487f-9ff0-e05dbbbbeb0c"/></modified><rdf:value xml:lang="en">changed cmeta id to be version aspecific, updated curation status,
removed reference link from documentation</rdf:value></rdf:Description><rdf:Description rdf:nodeID="n2"><rdf:_1 xml:lang="en">zinc homeostasis</rdf:_1><rdf:_3 xml:lang="en">electrophysiology</rdf:_3><rdf:_2 xml:lang="en">yeast</rdf:_2><rdf:type><rdf:Description rdf:about="http://www.w3.org/1999/02/22-rdf-syntax-ns#Bag"/></rdf:type></rdf:Description><rdf:Description rdf:about="rdf:#72f2ffc1-9066-4c1d-ad2f-b2e5baabdb5f"><N xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#3d6a53cd-ac83-4b55-ad42-6be346efd7a7"/></N></rdf:Description><rdf:Description rdf:about="rdf:#f2a151f3-7a15-41e8-bbb0-86927d31b486"><rdf:type><rdf:Description rdf:about="http://www.cellml.org/bqs/1.0#Person"/></rdf:type><N xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#e04f613b-13aa-4bc7-8fa3-c877431efc29"/></N></rdf:Description><rdf:Description rdf:about="#Py1"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Py1</title><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">active Zur</alternative><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">Zur dimer containing two zinc ions per monomer</alternative><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">Zn4Zur</alternative></rdf:Description><rdf:Description rdf:about="rdf:#a12fd43c-1184-49af-8cde-b7e6d08757e5"><rdf:type><rdf:Description rdf:about="http://imc.org/vCard/3.0#internet"/></rdf:type><rdf:value xml:lang="en">c.lloyd@auckland.ac.nz</rdf:value></rdf:Description><rdf:Description rdf:about="rdf:#03f0f646-71aa-470c-be97-560513f58350"><W3CDTF xmlns="http://purl.org/dc/terms/" xml:lang="en">2008-10-24 00:00</W3CDTF></rdf:Description><rdf:Description rdf:nodeID="n4"><subject xmlns="http://purl.org/dc/elements/1.1/"><rdf:Description rdf:nodeID="n1"/></subject></rdf:Description><rdf:Description rdf:about="rdf:#ab2dca7f-740c-43db-bc4e-ad1aee3d1122"><rdf:_1><rdf:Description rdf:about="rdf:#f2a151f3-7a15-41e8-bbb0-86927d31b486"/></rdf:_1><rdf:_3><rdf:Description rdf:about="rdf:#fe682b50-c2f1-408e-aa1d-af29c209b795"/></rdf:_3><rdf:_2><rdf:Description rdf:about="rdf:#650ea023-73db-4668-a4db-cb88774b57c6"/></rdf:_2><rdf:type><rdf:Description rdf:about="http://www.w3.org/1999/02/22-rdf-syntax-ns#Seq"/></rdf:type></rdf:Description><rdf:Description rdf:about="rdf:#6af6c154-b9f3-487f-9ff0-e05dbbbbeb0c"><W3CDTF xmlns="http://purl.org/dc/terms/" xml:lang="en">2009-06-08T15:38:35+12:00</W3CDTF></rdf:Description><rdf:Description rdf:about="rdf:#e04f613b-13aa-4bc7-8fa3-c877431efc29"><Given xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Jiangjun</Given><Family xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Cui</Family></rdf:Description><rdf:Description rdf:nodeID="n5"><boundIntervals xmlns="http://www.cellml.org/metadata/simulation/1.0#"><rdf:Description rdf:nodeID="n6"/></boundIntervals></rdf:Description><rdf:Description rdf:about=""><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Model does not include the zinc-buffering effects of TPEN</title><creator xmlns="http://purl.org/dc/elements/1.1/"><rdf:Description rdf:about="rdf:#8a960c2a-c071-448c-a98d-672b6561f75c"/></creator><publisher xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en"></publisher><cmeta:comment><rdf:Description rdf:about="rdf:#fc2f7f62-4eab-4c67-a73d-8e2d1c22f132"/></cmeta:comment><cmeta:modification><rdf:Description rdf:about="rdf:#f13c6b6e-0e1a-4261-87b6-ab969e7ebe7f"/></cmeta:modification><created xmlns="http://purl.org/dc/terms/"><rdf:Description rdf:about="rdf:#8867d5ff-ca9d-4bd2-ab6a-c7ffee3a202f"/></created></rdf:Description><rdf:Description rdf:about="#Qw1"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Qw1</title><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">transcription initiation complex of ZnuC</alternative></rdf:Description><rdf:Description rdf:about="#Qz1"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Qz1</title><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">transcription initiation complex formed by Dz and Rz</alternative></rdf:Description><rdf:Description rdf:about="#Mw"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">Mw</title><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">mRNA of ZnuC</alternative></rdf:Description><rdf:Description rdf:about="rdf:#8a960c2a-c071-448c-a98d-672b6561f75c"><EMAIL xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#a12fd43c-1184-49af-8cde-b7e6d08757e5"/></EMAIL><ORG xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#8b6e0f70-ccbf-4618-970f-a2f74209f8a7"/></ORG><N xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#3fd2ed4a-2d7e-4c83-a7e6-dc3fa380b55c"/></N></rdf:Description></rdf:RDF></model>
