y_petri 1.0.0

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data/.gitignore

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+*~
+.#*
+\#*#
+*.gem
+*.rbc
+.bundle
+.config
+.yardoc
+Gemfile.lock
+InstalledFiles
+_yardoc
+coverage
+doc/
+lib/bundler/man
+pkg
+rdoc
+spec/reports
+test/tmp
+test/version_tmp
+tmp

data/Gemfile

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+source 'https://rubygems.org'
+
+# Specify your gem's dependencies in y_petri.gemspec
+gemspec

data/LICENSE

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+Copyright (c) 2012 boris
+
+MIT License
+
+Permission is hereby granted, free of charge, to any person obtaining
+a copy of this software and associated documentation files (the
+"Software"), to deal in the Software without restriction, including
+without limitation the rights to use, copy, modify, merge, publish,
+distribute, sublicense, and/or sell copies of the Software, and to
+permit persons to whom the Software is furnished to do so, subject to
+the following conditions:
+
+The above copyright notice and this permission notice shall be
+included in all copies or substantial portions of the Software.
+
+THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND,
+EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF
+MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND
+NONINFRINGEMENT. IN NO EVENT SHALL THE AUTHORS OR COPYRIGHT HOLDERS BE
+LIABLE FOR ANY CLAIM, DAMAGES OR OTHER LIABILITY, WHETHER IN AN ACTION
+OF CONTRACT, TORT OR OTHERWISE, ARISING FROM, OUT OF OR IN CONNECTION
+WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN THE SOFTWARE.

data/README.md

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+# YPetri
+
+y_petri is a Petri net domain model and simulator
+
+## Installation
+
+Add this line to your application's Gemfile:
+
+    gem 'y_petri'
+
+And then execute:
+
+    $ bundle
+
+Or install it yourself as:
+
+    $ gem install y_petri
+
+## Usage
+
+y_petri can be used either interactively (in irb with
+'include YPetri'), or from another program. YPetri::Manipulator
+provides the command interface.
+
+## Contributing
+
+1. Fork it
+2. Create your feature branch (`git checkout -b my-new-feature`)
+3. Commit your changes (`git commit -am 'Added some feature'`)
+4. Push to the branch (`git push origin my-new-feature`)
+5. Create new Pull Request

data/Rakefile

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+#!/usr/bin/env rake
+require "bundler/gem_tasks"

data/lib/y_petri/demonstrator.rb

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+#encoding: utf-8
+
+require 'y_petri'
+include YPetri
+
+# general assumptions
+Cytoplasm_volume_in_litres = 5.0e-11
+NA = 6.022e23
+Pieces_per_micromolar = NA / 1_000_000 * Cytoplasm_volume_in_litres
+
+# simulation settings
+set_step 60
+set_target_time 60 * 60 * 24
+
+# places
+AMP = Place m!: 8695.0
+ADP = Place m!: 6521.0
+ATP = Place m!: 3152.0
+Deoxycytidine = Place( m!: 0.5 )
+DeoxyCTP = Place( m!: 1.0 )
+DeoxyGMP = Place( m!: 1.0 )
+U12P = Place( m!: 2737.0 )
+DeoxyUMP_DeoxyUDP_pool = Place( m!: 0.0 )
+DeoxyTMP = Place( m!: 3.3 )
+DeoxyTDP_DeoxyTTP_pool = Place( m!: 5.0 )
+Thymidine = Place( m!: 0.5 )
+TK1 = Place( m!: 100_000 )
+TYMS = Place( m!: 100_000 )
+RNR = Place( m!: 100_000 )
+TMPK = Place( m!: 100_000 )
+
+# molecular masses
+TK1_kDa = 24.8
+TYMS_kDa = 66.0
+RNR_kDa = 140.0
+TMPK_kDa = 50.0
+
+# enzyme specific activities
+TK1_a = 5.40
+TYMS_a = 3.80
+RNR_a = 1.00
+TMPK_a = 0.83
+
+# clamps
+clamp AMP: 8695.0, ADP: 6521.0, ATP: 3152.0
+clamp Deoxycytidine: 0.5, DeoxyCTP: 1.0, DeoxyGMP: 1.0
+clamp Thymidine: 0.5
+clamp U12P: 2737.0
+
+# functions
+Vmax_per_minute_per_enzyme_molecule =
+  lambda { |enzyme_specific_activity_in_micromol_per_minute_per_mg,
+            enzyme_molecular_mass_in_kDa|
+              enzyme_specific_activity_in_micromol_per_minute_per_mg *
+                enzyme_molecular_mass_in_kDa }
+Vmax_per_minute =
+  lambda { |specific_activity, kDa, enzyme_molecules_per_cell|
+           Vmax_per_minute_per_enzyme_molecule.( specific_activity, kDa ) *
+             enzyme_molecules_per_cell }
+Vmax_per_second =
+  lambda { |specific_activity, kDa, enzyme_molecules_per_cell|
+           Vmax_per_minute.( specific_activity,
+                             kDa,
+                             enzyme_molecules_per_cell ) / 60 }
+Km_reduced =
+  lambda { |km, ki_hash={}|
+           ki_hash.map { |concentration, ci_Ki|
+                         concentration / ci_Ki
+                       }.reduce( 1, :+ ) * km }
+Occupancy =
+  lambda { |concentration, reactant_Km, compet_inh_w_Ki_hash={}|
+           concentration / ( concentration +
+                             Km_reduced.( reactant_Km,
+                                          compet_inh_w_Ki_hash ) ) }
+MM_with_inh_micromolars_per_second =
+  lambda { |reactant_concentration,
+            enzyme_specific_activity,
+            enzyme_mass_in_kDa,
+            enzyme_molecules_per_cell,
+            reactant_Km,
+            competitive_inh_w_Ki_hash={}|
+            Vmax_per_second.( enzyme_specific_activity,
+                              enzyme_mass_in_kDa,
+                              enzyme_molecules_per_cell ) *
+              Occupancy.( reactant_concentration,
+                          reactant_Km,
+                          competitive_inh_w_Ki_hash ) }
+MMi = MM_with_inh_micromolars_per_second
+
+# michaelis constants
+TK1_Thymidine_Km = 5.0
+TYMS_DeoxyUMP_Km = 2.0
+RNR_UDP_Km = 1.0
+TMPK_DeoxyTMP_Km = 12.0
+
+# DNA synthesis speed
+DNA_creation_speed = 3_000_000_000 / ( 12 * 3600 )
+
+# transitions
+Transition name: :TK1_Thymidine_DeoxyTMP,
+           domain: [ Thymidine,
+                     TK1,
+                     DeoxyTDP_DeoxyTTP_pool,
+                     DeoxyCTP,
+                     Deoxycytidine,
+                     AMP,
+                     ADP,
+                     ATP ],
+           stoichiometry: { Thymidine: -1,
+                            DeoxyTMP: 1 },
+           rate: proc { |rc, e, pool1, ci2, ci3, master1, master2, master3|
+                        ci1 = pool1 * master3 / ( master2 + master3 )
+                        MMi.( rc, TK1_a, TK1_kDa, e, TK1_Thymidine_Km,
+                              ci1 => 13.5, ci2 => 0.8, ci3 => 40.0 )
+                      }
+Transition name: :TYMS_DeoxyUMP_DeoxyTMP,
+           domain: [ DeoxyUMP_DeoxyUDP_pool,
+                     TYMS,
+                     AMP,
+                     ADP,
+                     ATP ],
+           stoichiometry: { DeoxyUMP_DeoxyUDP_pool: -1,
+                            DeoxyTMP: 1 },
+           rate: proc { |pool, e, master1, master2, master3|
+                        rc = pool * master2 / ( master1 + master2 )
+                        MMi.( rc, TYMS_a, TYMS_kDa, e, TYMS_DeoxyUMP_Km )
+                      }
+Transition name: :RNR_UDP_DeoxyUDP,
+           domain: [ U12P,
+                     RNR, DeoxyUMP_DeoxyUDP_pool,
+                     AMP,
+                     ADP,
+                     ATP ],
+              stoichiometry: { U12P: -1,
+                               DeoxyUMP_DeoxyUDP_pool: 1 },
+              rate: proc { |pool, e, master1, master2, master3|
+                           rc = pool * master2 / ( master1 + master2 )
+                           MMi.( rc, RNR_a, RNR_kDa, e, RNR_UDP_Km )
+                         }
+Transition name: :DNA_polymerase_consumption_of_DeoxyTTP,
+           stoichiometry: { DeoxyTDP_DeoxyTTP_pool: -1 },
+           rate: proc { DNA_creation_speed / 4 }
+Transition name: :TMPK_DeoxyTMP_DeoxyTDP,
+           domain: [ DeoxyTMP,
+                     TMPK,
+                     ADP,
+                     DeoxyTDP_DeoxyTTP_pool,
+                     DeoxyGMP,
+                     AMP,
+                     ATP ],
+           stoichiometry: { DeoxyTMP: -1,
+                            TMPK: 0,
+                            DeoxyTDP_DeoxyTTP_pool: 1 },
+           rate: proc { |rc, e, ci1, pool, ci4, master1, master3|
+                        master2 = ci1
+                        ci2 = pool * master2 / ( master2 + master3 )
+                        ci3 = pool * master3 / ( master2 + master3 )
+                        MMi.( rc, TMPK_a, TMPK_kDa, e, TMPK_DeoxyTMP_Km,
+                              ci1 => 250.0, ci2 => 30.0, ci3 => 750, ci4 => 117 )
+                      }
+
+# execution
+run!
+plot_recording

data/lib/y_petri/demonstrator_2.rb

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+#encoding: utf-8
+
+require 'y_petri'
+include YPetri
+require 'sy'
+
+
+# === General assumptions
+
+Cytoplasm_volume = 5.0e-11.l
+Pieces_per_concentration = SY::Nᴀ * Cytoplasm_volume
+
+
+# === Simulation settings
+
+set_step 60.s
+set_target_time 20.min
+set_sampling 120.s
+
+
+# === Places
+
+AMP = Place m!: 8695.0.µM
+ADP = Place m!: 6521.0.µM
+ATP = Place m!: 3152.0.µM
+Deoxycytidine = Place m!: 0.5.µM
+DeoxyCTP = Place m!: 1.0.µM
+DeoxyGMP = Place m!: 1.0.µM
+U12P = Place m!: 2737.0.µM
+DeoxyU12P = Place m!: 0.0.µM
+DeoxyTMP = Place m!: 3.3.µM
+DeoxyT23P = Place m!: 5.0.µM
+Thymidine = Place m!: 0.5.µM
+TK1 = Place m!: 100_000.unit.( SY::MoleAmount ) / Cytoplasm_volume
+TYMS = Place m!: 100_000.unit.( SY::MoleAmount ) / Cytoplasm_volume
+RNR = Place m!: 100_000.unit.( SY::MoleAmount ) / Cytoplasm_volume
+TMPK = Place m!: 100_000.unit.( SY::MoleAmount ) / Cytoplasm_volume
+
+
+# === Enzyme molecular masses
+
+TK1_m = 24.8.kDa
+TYMS_m = 66.0.kDa
+RNR_m = 140.0.kDa
+TMPK_m = 50.0.kDa
+
+
+# === Specific activities of the enzymes
+
+TK1_a = 5.40.µmol.min⁻¹.mg⁻¹
+TYMS_a = 3.80.µmol.min⁻¹.mg⁻¹
+RNR_a = 1.00.µmol.min⁻¹.mg⁻¹
+TMPK_a = 0.83.µmol.min⁻¹.mg⁻¹
+
+
+# === Clamps
+
+clamp AMP: 8695.0.µM, ADP: 6521.0.µM, ATP: 3152.0.µM
+clamp Deoxycytidine: 0.5.µM, DeoxyCTP: 1.0.µM, DeoxyGMP: 1.0.µM
+clamp Thymidine: 0.5.µM
+clamp U12P: 2737.0.µM
+
+
+# === Function closures
+
+# Vmax of an enzyme.
+# 
+Vmax_enzyme = lambda { |specific_activity, mass, enz_conc|
+  specific_activity * mass * enz_conc.( SY::Molecularity )
+}
+
+# Michaelis constant reduced for competitive inhibitors.
+# 
+Km_reduced = lambda { |km, ki_hash={}|
+  ki_hash.map { |concentration, ci_Ki| concentration / ci_Ki }
+    .reduce( 1, :+ ) * km
+}
+
+# Occupancy of enzyme active sites at given concentration of reactants
+# and competitive inhibitors.
+# 
+Occupancy = lambda { |reactant_conc, reactant_Km, ci_Ki={}|
+  reactant_conc / ( reactant_conc + Km_reduced.( reactant_Km, ci_Ki ) )
+}
+
+# Michaelis and Menten equation with competitive inhibitors.
+# 
+MMi = MM_equation_with_inhibitors = lambda {
+  |reactant_conc, enz_spec_act, enz_mass, enz_conc, r_Km, ci_Ki={}|
+  Vmax_enzyme.( enz_spec_act, enz_mass, enz_conc ) *
+    Occupancy.( reactant_conc, r_Km, ci_Ki )
+}
+
+
+# === Michaelis constants of the enzymes involved.
+
+TK1_Thymidine_Km = 5.0.µM
+TYMS_DeoxyUMP_Km = 2.0.µM
+RNR_UDP_Km = 1.0.µM
+TMPK_DeoxyTMP_Km = 12.0.µM
+
+
+# === DNA synthesis speed.
+
+DNA_creation_speed =
+  3_000_000_000.unit.( SY::MoleAmount ) / 12.h / Cytoplasm_volume
+
+
+# === Transitions
+
+# Synthesis of TMP by TK1.
+# 
+TK1_Thymidine_DeoxyTMP = Transition s: { Thymidine: -1, DeoxyTMP: 1 },
+  domain: [ Thymidine, TK1, DeoxyT23P, DeoxyCTP, Deoxycytidine, AMP, ADP, ATP ],
+    rate: proc { |rc, e, pool1, ci2, ci3, master1, master2, master3|
+            ci1 = pool1 * master3 / ( master2 + master3 )
+            MMi.( rc, TK1_a, TK1_m, e, TK1_Thymidine_Km,
+                  ci1 => 13.5.µM, ci2 => 0.8.µM, ci3 => 40.0.µM )
+          }
+
+# Methylation of DeoxyUMP into TMP by TYMS.
+# 
+TYMS_DeoxyUMP_DeoxyTMP = Transition s: { DeoxyU12P: -1, DeoxyTMP: 1 },
+  domain: [ DeoxyU12P, TYMS, AMP, ADP, ATP ],
+    rate: proc { |pool, e, master1, master2, master3|
+            rc = pool * master2 / ( master1 + master2 )
+            MMi.( rc, TYMS_a, TYMS_m, e, TYMS_DeoxyUMP_Km )
+          }
+
+# Reduction of UDP into DeoxyUDP by RNR.
+# 
+RNR_UDP_DeoxyUDP = Transition s: { U12P: -1, DeoxyU12P: 1 },
+  domain: [ U12P, RNR, DeoxyU12P, AMP, ADP, ATP ],
+    rate: proc { |pool, e, master1, master2, master3|
+            rc = pool * master2 / ( master1 + master2 )
+            MMi.( rc, RNR_a, RNR_m, e, RNR_UDP_Km )
+          }
+
+# Consumption of TTP by DNA synthesis.
+# 
+DeoxyTTP_to_DNA = Transition s: { DeoxyT23P: -1 },
+    rate: proc { DNA_creation_speed / 4 }
+
+# Phosphorylation of TMP into TDP-TTP pool.
+# 
+TMPK_DeoxyTMP_DeoxyTDP = Transition s: { DeoxyTMP: -1, TMPK: 0, DeoxyT23P: 1 },
+  domain: [ DeoxyTMP, TMPK, ADP, DeoxyT23P, DeoxyGMP, AMP, ATP ],
+    rate: proc { |rc, e, ci1, pool, ci4, master1, master3|
+            master2 = ci1
+            ci2 = pool * master2 / ( master2 + master3 )
+            ci3 = pool * master3 / ( master2 + master3 )
+            MMi.( rc, TMPK_a, TMPK_m, e, TMPK_DeoxyTMP_Km,
+                  ci1 => 250.0.µM, ci2 => 30.0.µM, ci3 => 750.µM, ci4 => 117.µM )
+          }
+
+# TMPK_DeoxyTMP_DeoxyTDP = SR_transition DeoxyTMP: -1, TMPK: 0, DeoxyT23P: 1 do
+#   MMi.( DeoxyTMP, TMPK_a, TMPK_m, TMPK, TMPK_DeoxyTMP_Km,
+#         ADP => 250.0.µM,
+#         ( DeoxyT23P * ADP / ( ADP + ATP ) ) => 30.0.µM,
+#         ( DeoxyT23P * ATP / ( ADP + ATP ) ) => 750.µM,
+#         DeoxyGMP => 117.µM )
+# end
+
+# RubyVM::InstructionSequence.disassemble( block )
+# # and then process it to reconstruct the domain and construct the real closure
+
+
+# === Simulation execution
+
+# YPetri::DEBUG = true
+run!
+
+
+# === Plotting of the results
+
+plot_recording

data/lib/y_petri/demonstrator_3.rb

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+#encoding: utf-8
+
+require 'y_petri'
+include YPetri
+require 'sy'
+require 'mathn'
+
+# === General assumptions
+
+Cell_diameter = 10.µm
+Cytoplasm_volume = ( 4 / 3 * Math::PI * ( Cell_diameter / 2 ) ** 3 ).( SY::LitreVolume )
+# Cytoplasm_volume = 5.0e-11.l         # of an average cell
+# How many molecules are there in the average cell per micromolar.
+Pieces_per_µM = ( 1.µM * Cytoplasm_volume ).in( :unit )
+
+# === Simulation settings
+
+set_step 60.s.in( :s )
+set_target_time 20.min.in( :s )
+set_sampling 120.s.in( :s )
+
+# === Places (all in µM)
+
+AMP = Place m!: 8695.0
+ADP = Place m!: 6521.0
+ATP = Place m!: 3152.0
+DeoxyCytidine = Place m!: 0.5
+DeoxyCTP = Place m!: 1.0
+DeoxyGMP = Place m!: 1.0
+U12P = Place m!: 2737.0
+DeoxyU12P = Place m!: 0.0
+DeoxyTMP = Place m!: 3.3
+DeoxyT23P = Place m!: 5.0
+Thymidine = Place m!: 0.5
+TK1 = Place m!: 100_000 / Pieces_per_µM
+TYMS = Place m!: 100_000 / Pieces_per_µM
+RNR = Place m!: 100_000 / Pieces_per_µM
+TMPK = Place m!: 100_000 / Pieces_per_µM
+
+# === Molecular masses
+
+TK1_m = 24.8.kDa
+TYMS_m = 66.0.kDa
+RNR_m = 140.0.kDa
+TMPK_m = 50.0.kDa
+
+# === Enzyme specific activities
+
+TK1_a = 5.40.µmol.min⁻¹.mg⁻¹
+TYMS_a = 3.80.µmol.min⁻¹.mg⁻¹
+RNR_a = 1.00.µmol.min⁻¹.mg⁻¹
+TMPK_a = 0.83.µmol.min⁻¹.mg⁻¹
+
+# === Enzyme kcat
+
+TK1_k_cat = ( TK1_a * TK1_m ).( SY::Amount / SY::Time ).in :s⁻¹
+TYMS_k_cat = ( TYMS_a * TYMS_m ).( SY::Amount / SY::Time ).in :s⁻¹
+RNR_k_cat = ( RNR_a * RNR_m ).( SY::Amount / SY::Time ).in :s⁻¹
+TMPK_k_cat = ( TMPK_a * TMPK_m ).( SY::Amount / SY::Time ).in :s⁻¹
+
+# === Clamps (all in µM)
+
+clamp AMP: 8695.0, ADP: 6521.0, ATP: 3152.0
+clamp DeoxyCytidine: 0.5, DeoxyCTP: 1.0, DeoxyGMP: 1.0
+clamp Thymidine: 0.5
+clamp U12P: 2737.0
+
+# === Function closures
+
+# Vmax of an enzyme.
+# 
+Vmax = -> enzyme_µM, k_cat do enzyme_µM * k_cat end
+
+# Michaelis constant reduced for competitive inhibitors.
+# 
+Km_reduced = -> reactant_Km, hash_Ki=Hash.new do
+  hash_Ki.map { |compet_inhibitor_concentration, compet_inhibitor_Ki|
+    compet_inhibitor_concentration / compet_inhibitor_Ki
+  }.reduce( 1, :+ ) * reactant_Km
+end
+
+# Occupancy fraction of the Michaelis-Menten equation.
+# 
+Occupancy = -> reactant_µM, reactant_Km, hash_Ki=Hash.new do
+  reactant_µM / ( reactant_µM + Km_reduced.( reactant_Km, hash_Ki ) )
+end
+
+# Michaelis-Menten equation with competitive inhibitors.
+# 
+MMi = -> reactant_µM, reactant_Km, enzyme_µM, k_cat, hash_Ki=Hash.new do
+  Vmax.( enzyme_µM, k_cat ) * Occupancy.( reactant_µM, reactant_Km, hash_Ki )
+end
+
+# === Michaelis constants (all in µM)
+
+TK1_Thymidine_Km = 5.0
+TYMS_DeoxyUMP_Km = 2.0
+RNR_UDP_Km = 1.0
+TMPK_DeoxyTMP_Km = 12.0
+
+# === DNA synthesis speed
+
+S_phase_duration = 12.h
+Genome_size = 3_000_000_000          # of bases
+DNA_creation_speed = Genome_size / S_phase_duration.in( :s ) # in base.s⁻¹
+
+# === Transitions
+
+Transition name: :TK1_Thymidine_DeoxyTMP,
+           domain: [ Thymidine, TK1, DeoxyT23P, DeoxyCTP, DeoxyCytidine, AMP, ADP, ATP ],
+           stoichiometry: { Thymidine: -1, DeoxyTMP: 1 },
+           rate: proc { |reactant, enzyme, pool, inhibitor_2, inhibitor_3, mono, di, tri|
+             inhibitor_1 = pool * tri / ( di + tri ) # conc. of DeoxyTTP
+             MMi.( reactant, TK1_Thymidine_Km, enzyme, TK1_k_cat,
+                   inhibitor_1 => 13.5, inhibitor_2 => 0.8, inhibitor_3 => 40.0 )
+           }
+
+Transition name: :TYMS_DeoxyUMP_DeoxyTMP,
+           domain: [ DeoxyU12P, TYMS, AMP, ADP, ATP ],
+           stoichiometry: { DeoxyU12P: -1, DeoxyTMP: 1 },
+           rate: proc { |pool, enzyme, mono, di, tri|
+             reactant = pool * di / ( mono + di ) # conc. of DeoxyUMP
+             MMi.( reactant, TYMS_DeoxyUMP_Km, enzyme, TYMS_k_cat )
+           }
+
+Transition name: :RNR_UDP_DeoxyUDP,
+           domain: [ U12P, RNR, DeoxyU12P, AMP, ADP, ATP ],
+           stoichiometry: { U12P: -1, DeoxyU12P: 1 },
+           rate: proc { |pool, enzyme, mono, di, tri|
+             reactant = pool * di / ( mono + di )
+             MMi.( reactant, RNR_UDP_Km, enzyme, RNR_k_cat )
+           }
+
+Transition name: :DNA_polymerase_consumption_of_DeoxyTTP,
+           stoichiometry: { DeoxyT23P: -1 },
+           rate: proc { DNA_creation_speed / 4 }
+
+Transition name: :TMPK_DeoxyTMP_DeoxyTDP,
+           domain: [ DeoxyTMP, TMPK, DeoxyT23P, DeoxyGMP, AMP, ADP, ATP ],
+           stoichiometry: { DeoxyTMP: -1, DeoxyT23P: 1 },
+           rate: proc { |reactant, enzyme, pool, inhibitor_4, mono, di, tri|
+             inhibitor_1 = di
+             inhibitor_2 = pool * di / ( di + tri ) # conc. of DeoxyTDP
+             inhibitor_3 = pool * tri / ( di + tri ) # conc. of DeoxyTTP
+             MMi.( reactant, TMPK_DeoxyTMP_Km, enzyme, TMPK_k_cat )
+           }
+
+# execution
+run!
+plot_recording