Cellular Respiration: Mitochondrial Electron Transport Chain

;; Cellular Respiration: Mitochondrial Electron Transport Chain
;;
;; Coded in 2019 by Lin Xiang (lin.xiang@uky.edu), based on the ElectronTransport model initially developed by Steven Brewer.
;;
;; Brewer, S.D. (2004).  Electron Transport: Simulating Proton Gradient, ADP-ATP, and NADH-NAD+ Interactions.
;; http://bcrc.bio.umass.edu/netlogo/models/ElectronTransport/Biology Computer Resource Center. (lxiang75@gmail.com; lin.xiang@uky.edu)
;;
;; If you mention this model in a publication, we ask that you include the citations below.
;;
;; Xiang, L. (2019). Cellular Respiration: Mitochondrial Electron Transport Chain. Department of STEM Education, University of Kentucky, Lexington, KY.
;;
;;-----------------------------------------
;;CREATIVE COMMONS LICENSE
;;This code is distributed by Lin Xiang under a Creative Commons License:
;;Attribution-ShareAlike 4.0 International (CC BY-SA 4.0)
;;https://creativecommons.org/licenses/by-sa/4.0/
;;
;;-----------------------------------------

breed [enzymes enzyme]
breed [hs h]
breed [adps adp]
breed [nads nad]
breed [water a-water]
breed [oxygens oxygen]
breed [lipids lipid]
breed [poison1s poison1]
breed [poison2s poison2]

patches-own[protein]
hs-own [pass]

globals [n n1 atp]

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;;                                                                           ;;
;;         Main Procedures (SETUP and GO)                                    ;;
;;                                                                           ;;
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to setup
 ca

 set atp 100   ;have some ATPs to survive

 setup-membrane
 setup-NADH
 setup-oxygen
 setup-protons

reset-ticks
end 

to go
tick

  nad-nadh-action
  H-movement
  H-gradient-inhabitor-uncoupler
  ATP-water-formation
  oxygen-water-move
  NADH-formation
  ATP-consumption
  ;no-display
  plot-levels
  ;display

  if ATP <= 0 [user-message "The cell runs our of ATPs and dies." stop]
end 



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;;                                                                           ;;
;;         Sub-procedures of SETUP                                           ;;
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to setup-membrane

;make the inner membrane
  ask patches with [abs pycor <= 3] [set pcolor 49 ]

; make boundary for the system
  ask patches with [abs pxcor = max-pxcor or abs pycor = max-pycor] [set pcolor 2]

  ;add enzymes into the membrane
  ask patches with [pcolor = 49] [

    if pxcor >= -10 and pxcor <= -8 or
       pxcor >= -2 and pxcor <= 0 or
       pxcor >= 6 and pxcor <= 8
    [set pcolor 115 set protein 2]     ;set up ETS.

    if pxcor = -6 or
       pxcor = 2 or
       pxcor = 10
    [set pcolor 72 set protein 1]      ;set up ATP synthase

    if pxcor = -12 or
       pxcor = -4 or
       pxcor = 4 or
       pxcor = 12
    [set pcolor 138 set protein 3]      ;set up leak proteins (such as ANT or UCP)

  ]

  ask patches with [ pycor = 3 and pcolor = 49] [sprout-lipids 1 [set color 7 set shape "lipid" set size 4 set heading 0 set ycor ycor - 1.5]]
  ask patches with [ pycor = -3 and pcolor = 49] [sprout-lipids 1 [set color 7 set shape "lipid" set size 4 set heading 180 set ycor ycor + 1.5]]  ;setup the bilayer
end 

to setup-protons
  create-hs 30
  [set color 25
    set shape "proton1"
    set size 0.6
  setup-position]
end 

to setup-oxygen
  create-oxygens 5 + random 3 [set size 2 set color white set shape "oxygen"  setup-position-1]
end 

to setup-position     ;random positions in both up and bottom black areas
 setxy random-xcor random-ycor
  if pcolor != 0 [setup-position]
end 

to setup-position-1       ;random positions in the bottom black area
 setxy random-xcor random-ycor
  if pcolor != 0 or ycor >= -4 [setup-position-1]
end 

to setup-NADH       ;make 100 NADH molecules at the beginning
  create-nads 100
  [set color 25
    set shape "nadh"
    set size 2.5
    setup-position-1]
end 

to setup-poison1s
  ask patches with [pcolor = 113 and pycor = -3]
   [sprout-poison1s 1[
    set size 1
    set color yellow
    set shape "p-1"
  ]]
end 

to setup-poison2s
  create-poison2s 8
   [set size 1
    set color yellow
    set shape "p-2"
    setup-position]
end 

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;;                                                                           ;;
;;         Sub-procedures of GO                                              ;;
;;                                                                           ;;
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to nad-nadh-action
  ask nads [right random 90 left random 90   ; ask NADHs
    ifelse [pcolor] of patch-at dx dy != 0 [ifelse [pcolor] of patch-at dx dy != 115 [set heading heading - 180] ; Turn back if approching to a structure but not an ETC,
      [if shape = "nadh" [set shape "nad" set color 3 set size 2 hatch-hs 1 [set color 25 set shape "proton1" set size 0.6 fd 1  set pass 0]]]]  ;if approaching to an ETC, change to NAD+ and release one H+
    [fd 1]
  ]
end 

to H-gradient-inhabitor-uncoupler        ;;Activate or deactivate ETC based on H+ gradient, inhabitor and uncouplers
  ask patches with [protein = 1] [          ;ask ATP synthase
    ifelse Poison_ATP_synthase = true             ;If poisoned
      [set pcolor 72]                       ;change pcolor to deactivate ATP synthase
      [ifelse count hs with [ycor > 3] - count hs with [ycor < -3] >= 10 [set pcolor 75][set pcolor 72]]   ; if not poisoned, stay activated if H+ gradient is established, deactivated if H+ gradient is too low.
      ]

  ask patches with [protein = 2] [          ;ask ETC
    ifelse Poison_ETC = true or block-oxygen = true   ;If poisoned or oxygen is blocked
    [set pcolor 113]                        ;change pcolor to deactivate ETC
    [ifelse count hs with [ycor > 3] / (1 + count hs with [ycor < -3]) >= 200 [set pcolor 113][set pcolor 115]]]; if not poisoned, stay activated if H+ gradient is not too high, deactivated if H+ gradient is too high.

  ask patches with [protein = 3] [          ;ask leak proteins
    ifelse Uncouplers = true                ;If uncoupled
      [set pcolor 137]                      ;change pcolor to activate uncouplers
      [set pcolor 138]                      ; change color to deavtiate uncouplers
      ]

  oxygen-factor
end 

to H-movement
  ask hs
  [
    if pcolor = 0
      [right random 90 left random 90   ;wiggle
         if [pcolor] of patch-at dx dy = 0 [fd 0.3]   ;If nothing is aheadm, move forward
         if [pcolor] of patch-at dx dy  = 75 [ifelse heading > 90 or heading < 270  [fd 1][set heading heading - 180]]  ;if an H+ gets close to an ATP synthase and if it is in the intermembrane space, bound with the ATP synthase
         if [pcolor] of patch-at dx dy = 115 [ifelse heading < 90 or heading > -90  [fd 1][set heading heading - 180]] ;if an H+ gets close to an ETC and it is in the matrix, bound with ETC complex
         if [pcolor] of patch-at dx dy = 137  [if heading > 90 or heading < 270  [ifelse uncouplers = true [fd 1][set heading heading - 180]]]  ;if an H+ gets close to an leak protein and it is in the intermembrane space, if uncouples are true, bound to the protein.
     ]

    if pcolor = 75 [set heading 180 fd 0.1       ;if a H+ has entered in an ATP synthase, move down into the matrix
      if ycor < -3 and pass = 1 [set pass 2]]    ;if a H+ go DOWN through the inner membrane, label its pass as 2


    if pcolor = 115 [set heading 0 fd 0.1          ;if a H+ has entered in an ETC complex, move up to the inter membrane space
      if ycor > 3 and pass = 0 [set pass 1]]       ;if a H+ go UP through the inner membrane, label its pass as 1


    if pcolor = 137 [set heading 180 fd 0.05      ;if a H+ has entered the bilayer, move down into the matrix
      if ycor < -3 and pass = 1 [set pass 2]]    ;if a H+ go DOWN through the inner membrane, label its pass as 2

    if ycor > 0 and pass = 2 [set pass 1]   ;some Hs may go back to inter membrane space, label the pass as 1 so it will not form water in the wrong place.
  ]
end 

to ATP-water-formation
  ask hs with [pass = 2 and pcolor = 75] [ if count oxygens > 0   ;ask Hs that pass through ATP synthase, if oxygens are present
    [hatch-water 1 [set shape "water" set color red set size 1.5 ] ;mostly of Hs form water molecule. Note Hs assumption and water formation are not in the ratio of 4:1.
      set atp atp + 3 die  ]]      ;Each H makes 3 ATPs

  ask hs with [pass = 2 and pcolor = 137] [ if count oxygens > 0   ;ask Hs that pass uncouplers, if oxygens are present
    [hatch-water 1 [set shape "water" set color red set size 1.5 ] ;mostly of Hs form water molecule. Note Hs assumption and water formation are not in the ratio of 4:1.
       die ]]      ;No ATPs are produced
end 

to oxygen-water-move       ;make water and oxygen only move within the matrix
  ask water [right random 90 left random 90
  ifelse [pcolor] of patch-at dx dy != 0
    [set heading heading - 180] [fd 0.3]]

  ask water [if [pcolor] of patch-at dx dy = 2 [die]]    ;if water gets to the boundary, disappears

  ask oxygens [right random 90 left random 90
  ifelse [pcolor] of patch-at dx dy != 0
    [set heading heading - 180] [fd 0.3]]
end 

to NADH-formation    ;reform NADH at an ajustable rate
  ask nads with [color = 3]
  [ if random 1000 < formation-of-NADH [
    ;if random-float 1 < (formation-of-NADH * 0.005) [
    set color 25
    set shape "nadh"
    set size 2.5]]
end 

to ATP-consumption
 if random 100 < ATP-consumption-rate [set atp atp - 1]
end 

to  oxygen-factor

  if block-oxygen = true [ask oxygens [die]]
  if block-oxygen = false [ if count oxygens <= 0 [create-oxygens 5 + random 3 [set size 2 set color white set shape "oxygen"  setup-position-1]]]
end 

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;;                                                                           ;;
;;         Supporting-procedures                                             ;;
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to plot-levels ;; this creates creates the bar graph
    set-current-plot "Proton Gradient"
    clear-plot
    plot-pen-down
    set-current-plot-pen "matrix"
    plotxy 1 count hs with [ycor <= -3]
    set-current-plot-pen "intermembrane"
    plotxy 2 count hs with [ycor >= 3]
end 


; Copyright 2019 by Lin Xiang.  All rights reserved.
;
; This model is modified based on the ElectronTransport model initially developed by Steven Brewer.
;
; Brewer, S.D. (2004).  Electron Transport: Simulating Proton Gradient,
; ADP-ATP, and NADH-NAD+ Interactions.
; http://bcrc.bio.umass.edu/netlogo/models/ElectronTransport/
; Biology Computer Resource Center