iTunesComputationalLab

breed [ LacIs LacI ]  ;; LacI repressior protein (violet proteins)
breed [ LacZs LacZ ]  ;; LacZ beta-galactosidase emzyme (red proteins)
breed [ ONPGs ONPG ]  ;; ortho-Nitrophenyl-beta-galactoside (ONPG) molecule (grey molecules) that is cleaved by beta-galactosidase to produce an intensely yellow compound.
breed [ LacYs LacY ]  ;; permease orange turtles that go to the cell wall and transport lactose inside
breed [ RNAPs RNAP ]  ;; RNA Polymerases (brown proteins) that bind to promoter part of DNA and synthesize mRNA from the downstream DNA

LacIs-own [
  partner             ;;  a partner is a ONPG molecule with which a LacI molecule binds to form a complex
  inhibitor?          ;;  a boolean to track if a LacI can bind to DNA as an inhibitor of transcition
]
RNAPs-own [on-dna?]   ;; a boolean to track if RNAP
ONPGs-own [
  partner             ;; a partner is a lacI molecule with which an ONPG forms a complex
]

globals
[ promoter-color-list       ;; color list to set promoter colors based on their strengths
  rbs-color-list            ;; color list to set rbs colors based on their strengths
  gene-color                ;; color of the gene
  operon-transcribed?       ;; a boolean to see if the operon is transcribed
  LACZ-PRODUCTION-NUM       ;; number of lacZ molecules produced per transcription (this number depends on the rbs strength)
  lacZ-production-num-list  ;; list of numbers to set lacZ molecules produced based on the rbs strength
  ONPG-degradation-count    ;; a variable to keep track of number of ONPG molecules degraded
  energy-value              ;; keeps track of the energy value of the cell
  lacI-number               ;; number of lacI molecules
  RNAP-number               ;; number of RNA Polemerase molecules
  inhibited?                ;; boolean for whether or not the operator is inhibited
  dna                       ;; agentset containing the patches that are DNA
  non-dna                   ;; agentset excluding the patches that are DNA
  lacZ-gene                 ;; agentset containing the patches that are LacZ gene
  promoter                  ;; agentset containing the patches that are for the promoter
  operator                  ;; agentset containing the patches that are for the operator
  rbs                       ;; agentset containing the patches that are for the rbs
  terminator                ;; agentset containing the patches that are for the terminator
  total-transcripts         ;; a variable to keep track of the number of transciption events
  total-proteins            ;; a veriable to keep track of the number of proteins produced
  ini-ONPG-number           ;; a veriable to set initial ONPG number. This number is set to 0 in the setup procedure. It is set to 200 in the 'Add ONPG' button.
]

to set-global-variables
  set promoter-color-list [62 64 65 68]
  set rbs-color-list [12 14 15 17]
  set gene-color 95
  set lacI-number 30
  set RNAP-number 30
  set lacZ-production-num-list [2 3 4 6]
  set inhibited? false
  set ONPG-degradation-count 0
  set total-transcripts 0
  set ini-ONPG-number 0
  set operon-transcribed? false
end 

to set-rbs-effect        ;; sets number of LacZ molecules produced per transcription event depedning on the rbs strength
   if rbs-strength = "weak" [
    set lacZ-production-num item 0 lacZ-production-num-list
  ]
  if rbs-strength = "reference" [
    set lacZ-production-num item 1 lacZ-production-num-list
  ]
  if rbs-strength = "medium" [
    set lacZ-production-num item 2 lacZ-production-num-list
  ]
  if rbs-strength = "strong" [
    set lacZ-production-num item 3 lacZ-production-num-list
  ]
end 

to setup
  ca
  set-global-variables
  set-rbs-effect
  set-DNA-patches
  add-proteins
  reset-ticks
end 

to go
  go-lacIs
  go-RNAPs
  go-LacZs
  if (operon-transcribed?) [
    create-lacZs lacZ-production-num [
      setxy random-xcor random-ycor
      setshape
    ]
    set total-proteins total-proteins + lacZ-production-num
    set operon-transcribed? false
  ]
  go-ONPGs
  degrade-lacZ
  dissociate-complex
  recolor-patches
  ask turtles [
    setshape
  ]
  if timed-expt? [
    if ticks = 2500 [ stop ]
  ]
  if const-ONPG? [
    add-ONPG ( ini-ONPG-number - count ONPGs )
  ]

  tick
end 

to random-walk    ;; a random walk procedure for the proteins and ONPG molecules in the cell
  rt random-float 360
  fd 1
end 

to set-DNA-patches   ;; a procedure to set the DNA patches in the cell and assign appropriate colors based on their strengths
  ask patches [set pcolor white]
  set dna patches with [
    pxcor >= -40 and pxcor < 30 and pycor > 3 and pycor < 6
  ]
  set promoter patches with [
    pxcor >= -40 and pxcor < -26 and pycor > 3 and pycor < 6
  ]
  set operator ( patch-set
    patches with [ pxcor >= -26 and pxcor < -20 and pycor = 4 ]
    patches with [ pxcor = -26 and pycor = 5 ]
    patches with [ pxcor = -24 and pycor = 5 ]
    patches with [ pxcor = -23 and pycor = 5 ]
    patches with [ pxcor = -21 and pycor = 5 ]
  )

  set rbs patches with [
    pxcor >= -20 and pxcor < -15 and pycor > 3 and pycor < 6
  ]
  set lacZ-gene patches with [
    pxcor >= -15 and pxcor < 25 and pycor > 3 and pycor < 6
  ]
  set terminator patches with [
     pxcor >= 25 and pxcor < 30 and pycor > 3 and pycor < 6
  ]
  ask promoter [
    if promoter-strength = "strong" [
      set pcolor item 0 promoter-color-list
    ]
    if promoter-strength = "medium" [
      set pcolor item 1 promoter-color-list
    ]
    if promoter-strength = "reference" [
      set pcolor item 2 promoter-color-list
    ]
    if promoter-strength = "weak" [
      set pcolor item 3 promoter-color-list
    ]
  ]
  ask operator [
    set pcolor orange
  ]
  ask rbs [
    if rbs-strength = "strong" [
      set pcolor item 0 rbs-color-list
    ]
    if rbs-strength = "medium" [
      set pcolor item 1 rbs-color-list
    ]
    if rbs-strength = "reference" [
      set pcolor item 2 rbs-color-list
    ]
    if rbs-strength = "weak" [
      set pcolor item 3 rbs-color-list
    ]
  ]
  ask lacZ-gene [
    set pcolor gene-color
  ]
   ask terminator [
    set pcolor gray
  ]
  set non-dna patches with [pcolor = white]
end 

to add-proteins        ;; part of the setup procedure to create and randomly place proteins inside the cell
  create-lacIs lacI-number [
    setxy random-xcor random-ycor
    set inhibitor? false
    set partner nobody
    setshape
  ]
  create-RNAPs RNAP-number [
    setxy random-xcor random-ycor
    set on-dna? false
    setshape
  ]
end 

to setshape        ;; a procedure to set shapes of the molecules
  if breed = LacIs
  [ set size 10
    ifelse partner = nobody
    [ set shape "laci"]
    [ set shape "laci-onpg-complex" set size 10 ]
  ]
  if breed = RNAPs
    [ set size 6
      set shape "RNAPol"
      set color brown]
  if breed = ONPGs
    [
      ifelse partner = nobody
      [
        set shape "pentagon"
        set color gray
        set hidden? false
      ]
      [
        set hidden? true
      ]
    ]
   if breed = LacZs
   [ set shape "protein"
     set color red
     set size 6]
end 

to go-lacIs
   ;; If there is a LacI at the operator, set the transcription is inhibited.
  if not inhibited? [
    ask LacIs with [ member? patch-ahead 2 operator and partner = nobody] [
      set inhibitor? true
      set inhibited? true
      set heading 0
      setxy -23 6
    ]
  ]

ask LacIs with [inhibitor?] [
  if (random-float 10 < lacI-bond-leakage) [
    set inhibitor? false
    set inhibited? false
    fd 3
  ]
]
  ask LacIs with [not inhibitor?] [
   random-walk
  ]

  ask LacIs [
    if partner != nobody [ stop ]
    set partner one-of (other ONPGs-here with [partner = nobody])
    if partner = nobody [ stop ]
    if [partner] of partner != nobody [ set partner nobody stop ]  ;; just in case two lacIs grab the same partner
    ifelse random-float 1 < complex-formation-chance
      [ ask partner [ set partner myself ]
        setshape
        ask partner [ setshape ]
        if (inhibitor?) [
          set inhibited? false
          set inhibitor? false
          fd 1
        ]
      ]
    [set partner nobody]
  ]
end 

to go-RNAPs    ;; If a RNAP is close or on the promoter (green) and the operator is open, change heading and move on the DNA towards the terminator.

if not inhibited? [
  ask RNAPs [
    if promoter-strength = "strong" [
      if member? patch-here promoter or member? patch-ahead 9 promoter [
        start-transcription
      ]
    ]
    if promoter-strength = "medium" [
      if member? patch-here promoter or member? patch-ahead 3 promoter [
        start-transcription
      ]
    ]
    if promoter-strength = "reference" [
      if member? patch-here promoter or member? patch-ahead 2 promoter [
        start-transcription
      ]
    ]
    if promoter-strength = "weak" [
      if member? patch-here promoter or member? patch-ahead 1 promoter [
        start-transcription
      ]
    ]
  ]
]

if any? RNAPS with [on-dna?] [
  ask RNAPs with [on-dna?] [
    fd 1
    if (member? patch-here terminator) [
      set operon-transcribed? true
      set on-dna? false
      rt random-float 360
      set total-transcripts total-transcripts + 1
    ]
  ]
]

ask RNAPs with [not on-dna?] [
  random-walk
]
end 

to start-transcription    ;; a procedure for RNAPs
  setxy xcor 5
  set heading 90
  set on-dna? true
end 

to add-ONPG [ONPG-number]
   create-ONPGs ONPG-number [
    set partner nobody
    setxy random-xcor random-ycor
    setshape
   ]
end 

to go-lacZs
  ask lacZs [
    rt random-float 360
    fd 1
    if count ONPGs-here != 0 [
      if random-float 1 < ONPG-degradation-chance
      [ ask one-of ONPGs-here [ die ]
        set ONPG-degradation-count ONPG-degradation-count + 1
      ]
    ]
  ]
end 

to go-ONPGs
  ask ONPGs [
    random-walk
  ]
end 

to recolor-patches  ;; Change the color of the cell based on ONPG degradation
  ask non-dna [
    set pcolor scale-color yellow ( 1000 - ONPG-degradation-count ) 0 1000
  ]
end 

to dissociate-complex  ;; Dissociate the LacI-ONPG complex
  ask LacIs with [partner != nobody] [
    if random-float 1 < complex-separation-chance [
    let temp-x xcor
    let temp-y xcor
    ask partner [
      set partner nobody
      setxy temp-x temp-y
      setshape
      fd 1
    ]
    set partner nobody
    setshape
    fd -1
   ]
  ]
end 

to degrade-LacZ
  ask LacZs [
    if random-float 1 < LacZ-degradation-chance [
      die
    ]
  ]
end 

to-report number-of-transcripts-per-tick
  report precision ( total-transcripts / ticks * 1000 ) 1
end 

to-report number-of-proteins-per-tick
  report precision ( total-proteins / ticks * 1000 ) 1
end