Gene Expression: Logical Promoter

globals [ dA dB dC Kd KB rbound-A rbound-B time A-exp B-exp C-exp]
turtles-own [age bound partner]
breed [ rna ]
breed [ a-protein ]
breed [ b-protein ]
breed [ c-protein ]

to setup
;; (for this model to work with NetLogo's new plotting features,
  ;; __clear-all-and-reset-ticks should be replaced with clear-all at
  ;; the beginning of your setup procedure and reset-ticks at the end
  ;; of the procedure.)
  __clear-all-and-reset-ticks
; setup variables
reset-counters
set rbound-A false ; set the bound state of the operon to false
set rbound-B false ; set the bound state of the operon to false
set dA 10 ; rate of protein A
set dB 10 ; rate of protein B
set dC 10 ; rate of protein C
set Kd 4 ; dissociation coefficient
set KB 100 ; binding coefficient


      ; create binding sites  
      ; red - A
      ask patches with [(pxcor = -13) and (pycor = 0)] [ set pcolor red set plabel "A" ]
      ; create "gene"
      ask patches with [(pxcor > -13) and (pxcor <= -5) and (pycor = 0)] [ set pcolor white ]

      ; blue - B
      ask patches with [(pxcor = -6) and (pycor = 0)] [ set pcolor blue set plabel "B" ]
      ; create "gene"
      ask patches with [(pxcor > -6) and (pxcor <= 0) and (pycor = 0)] [ set pcolor white ]
      
     ; blue - C
      ask patches with [(pxcor = 1) and (pycor = 0)] [ set pcolor gray set plabel "P" ]
      ask patches with [(pxcor = 2) and (pycor = 0)] [ set pcolor gray set plabel "P" ]
      ask patches with [(pxcor = 3) and (pycor = 0)] [ set pcolor green set plabel "C" ]
      ; create "gene"
      ask patches with [(pxcor > 3) and (pxcor <= 10) and (pycor = 0)] [ set pcolor white ]

      
      ; create ribosomes
      ask patches with [ ((pxcor < -12) or (pxcor > 13)) or ((pycor < -3) or (pycor > 5))] [ if random 10 = 1 [set pcolor cyan] ]
  plot-history
  plot-levels               
end 

to go 
  set time time + 1
; do gene transcription
ask patches [

  if (plabel = "A") [
    if (gene-A = true and random 100 < dA ) [
      sprout 1 [
        set A-exp A-exp + 1
        set breed rna
        set partner nobody
        set shape "rna"
        set color red
        set bound false
        set age random 30
        set heading random 360
        fd 2
      ]
    ]
  ]
  
  if (plabel = "B") [
    if (gene-B = true and random 100 < dB) [
      sprout 1 [
        set B-exp B-exp + 1
        set breed rna
        set partner nobody
        set shape "rna"
        set color blue
        set bound false
        set age random 30
        set heading random 360
        fd 2
      ]
    ]
  ]

;; this determines which gate the system emulates
if (plabel = "C" ) [
  if (condition = "3" ) [if (not (rbound-A = true and rbound-B = true) ) [ express-c] ]
  if (condition = "4" ) [if (rbound-A = false and rbound-B = false) [ express-c]]
  if (condition = "1" ) [if (rbound-A = true and rbound-B = true) [ express-c]]
  if (condition = "2" ) [if (rbound-A = true or rbound-B = true) [ express-c]]
  if (condition = "5" ) [if ((rbound-A = true or rbound-B = true) and not (rbound-A = true and rbound-B = true)) [ express-c]]
]
]

; this was a bit tricky to get the order of events right
ask a-protein [
    without-interruption [bind-site-a]]
    ask b-protein [
    without-interruption [bind-site-b]]
ask turtles 
    [wander ;; both rnas and proteins check to see if they bind and otherwise move around
     grow-old] ;; both also are recycled by the cell machinery after a while.
plot-history
plot-levels
end 

to express-c

  if ( random 100 < dC ) [
     sprout 1 [
       set C-exp C-exp + 1
       set breed rna
       set partner nobody
       set shape "rna"
       set color green
       set bound false
       set age random 30
       set heading random 360
       fd 2
     ]
   ]
end 
 
; bind repressor to lacZ operon

to bind-site-a
  if (rbound-A = false and partner = nobody)
  [if (random 100 < Kb and breed = a-protein) [
    set bound true 
    set rbound-A true 
    setxy 1 0  
    set heading 180]]
end 

to bind-site-b
  if (rbound-B = false and partner = nobody)
  [if (random 100 < Kb and breed = b-protein) [
    set bound true 
    set rbound-B true 
    setxy 2 0  
    set heading 180]]
end 

; unbind repressor from lacZ operon

to unbind-site
  if ((random 100 < Kd) or (partner != nobody)) [
    ifelse (color = red) [set rbound-A false] [set rbound-B false] 
    set bound false  
    setxy random world-width random world-height
]
end 

; have RNAs, proteins, and inducers move around the environment

to wander
  if (pcolor = cyan and shape = "rna") [  
    ;; this is the ribosome translating
    hatch 1 [
ifelse (color = blue) [set breed b-protein ] [ifelse (color = green) [set breed c-protein ] [set breed a-protein ]]         
    set shape "repressor"
    set bound false
    set age 0
    set heading random 360
    ]
  ] 
  ifelse (bound = true) [without-interruption [unbind-site]] [rt random 90 - random 90 fd 1 ]
end 

to grow-old ;; cells break down rnas and proteins after a while.  
   set age age + 1
   if (age > (40 + random 100))  [if (bound != true) [die] ]
end 

to plot-levels ;; this creates creates the bar graph 
    set-current-plot "Protein Concentrations"
    clear-plot
    set-current-plot-pen "A"
    plot-pen-down
    plotxy 1 count turtles with [breed = a-protein] 
    set-current-plot-pen "B"
    plot-pen-down
    plotxy 2 count turtles with [breed = b-protein] 
    set-current-plot-pen "C"
    plot-pen-down
    plotxy 3 count turtles with [breed = c-protein] 
end 

to plot-history ;; this creates the line graph
  set-current-plot "Concentration History"
    set-current-plot-pen "A"
  plot ( count turtles with [breed = a-protein]  )
    set-current-plot-pen "B"
  plot ( count turtles with [breed = b-protein]  )
    set-current-plot-pen "C"
  plot ( count turtles with [breed = c-protein]  )
end 

to reset-counters
set A-exp 0
set B-exp 0
set C-exp 0
set time 0
end 

; This model was created as part of the 2004 BioQUEST Curriculum Consortium
; Summer Workshop.  
;
; Copyright 2004 by Steven Brewer.  All rights reserved.
; This model was inspired by many of the sample Netlogo models and parts 
; were based on functions from the Enzyme Kinetics model.  (Wilensky, U. (2001).  
; NetLogo Enzyme Kinetics model. http://ccl.northwestern.edu/netlogo/models/EnzymeKinetics. 
; Center for Connected Learning and Computer-Based Modeling, Northwestern University, 
; Evanston, IL.) 
;
; Permission to use, modify or redistribute this model is hereby granted,
; provided that both of the following requirements are followed:
; a) this copyright notice is included.
; b) this model will not be redistributed for profit without permission
;    from the authors.
; Contact the authors for appropriate licenses for redistribution for
; profit.
;
; To refer to this model in academic publications, please use:
; Brewer, S.D. (2004).  Logical Promoter: Simulating Logical Gates Using
; a Model of Gene Expression.  http://bcrc.bio.umass.edu/netlogo/models/LogicalPromoter
; Biology Computer Resource Center
;
; In other publications, please use:
; Copyright 2004 by Steven Brewer.  All rights reserved.  See
; http://bcrc.bio.umass.edu/netlogo/models/LogicalPromoter
; for terms of use.