//genesis
// kkit Version 11 flat dumpfile
// Saved on Mon Jul 18 13:42:26 2005
include kkit {argv 1}
FASTDT = 0.0001
SIMDT = 0.001
CONTROLDT = 10
PLOTDT = 10
MAXTIME = 2000
TRANSIENT_TIME = 10
VARIABLE_DT_FLAG = 1
DEFAULT_VOL = 9e-20
VERSION = 11.0
setfield /file/modpath value /home2/bhalla/scripts/modules
kparms
//genesis
initdump -version 3 -ignoreorphans 1
simobjdump table input output alloced step_mode stepsize x y z
simobjdump xtree path script namemode sizescale
simobjdump xcoredraw xmin xmax ymin ymax
simobjdump xtext editable
simobjdump xgraph xmin xmax ymin ymax overlay
simobjdump xplot pixflags script fg ysquish do_slope wy
simobjdump group xtree_fg_req xtree_textfg_req plotfield expanded movealone \
link savename file version md5sum mod_save_flag x y z
simobjdump geometry size dim shape outside x y z
simobjdump kpool DiffConst CoInit Co n nInit mwt nMin vol slave_enable \
comptname xtree_fg_req xtree_textfg_req x y z
simobjdump kreac kf kb notes xtree_fg_req xtree_textfg_req x y z
simobjdump kenz CoComplexInit CoComplex nComplexInit nComplex vol k1 k2 k3 \
keepconc usecomplex notes xtree_fg_req xtree_textfg_req link x y z
simobjdump stim level1 width1 delay1 level2 width2 delay2 baselevel trig_time \
trig_mode notes xtree_fg_req xtree_textfg_req is_running x y z
simobjdump xtab input output alloced step_mode stepsize notes editfunc \
xtree_fg_req xtree_textfg_req baselevel last_x last_y is_running x y z
simobjdump kchan perm gmax Vm is_active use_nernst notes xtree_fg_req \
xtree_textfg_req x y z
simobjdump transport input output alloced step_mode stepsize dt delay clock \
kf xtree_fg_req xtree_textfg_req x y z
simobjdump proto x y z
simobjdump doqcsinfo filename accessname accesstype transcriber developer \
citation species tissue cellcompartment methodology sources \
model_implementation model_validation editfunc
simundump geometry /kinetics/geometry 0 9e-20 3 sphere "" -217 98 0
simundump geometry /kinetics/geometry[1] 0 1e-20 3 sphere "" -209 160 0
simundump kpool /kinetics/CaM-Ca4 1 0 0 0 0 0 0 0 54 0 /kinetics/geometry \
blue yellow -229.07 118.13 0
simundump kpool /kinetics/PP1-active 1 0 1.8 1.8 97.2 97.2 0 0 54 0 \
/kinetics/geometry cyan yellow -241 100 0
simundump kenz /kinetics/PP1-active/Deph-thr286 0 0 0 0 0 54 0.045397 10 2.5 \
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simundump kenz /kinetics/PP1-active/Deph-thr286b 0 0 0 0 0 54 0.045397 10 2.5 \
0 0 "" red cyan "" -261.55 124.86 0
simundump kenz /kinetics/PP1-active/Deph-thr305 0 0 0 0 0 54 0.045397 10 2.5 \
0 0 "" red cyan "" -257.55 124.86 0
simundump kenz /kinetics/PP1-active/Deph-thr286c 0 0 0 0 0 54 0.045397 10 2.5 \
0 0 "" red cyan "" -250.55 124.86 0
simundump kenz /kinetics/PP1-active/Deph-thr305a 0 0 0 0 0 54 0.045397 10 2.5 \
0 0 "" red cyan "" -253.55 124.86 0
simundump kpool /kinetics/Ca 1 0 0.08 0.08 4.32 4.32 0 0 54 0 \
/kinetics/geometry red black -244.66 120.79 0
simundump kpool /kinetics/PKA-active 1 0 0.018519 0.018519 1 1 0 0 54 0 \
/kinetics/geometry yellow black -246 94 0
simundump kenz /kinetics/PKA-active/PKA-phosph-I1 1 0 0 0 0 54 0.11111 36 9 0 \
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simundump kenz /kinetics/PKA-active/PKA-phosph-I1_PSD 0 0 0 0 0 54.001 \
0.11111 36 9 0 0 "" red 27 "" -304 130 0
simundump group /kinetics/CaMKII 1 purple black x 0 0 "" defaultfile \
defaultfile.g 0 0 0 -249 141 0
simundump kpool /kinetics/CaMKII/CaMKII 1 0 20 20 1080 1080 0 0 54 0 \
/kinetics/geometry 1 purple -257 141 0
simundump kpool /kinetics/CaMKII/CaMKII-CaM 1 0 0 0 0 0 0 0 54 0 \
/kinetics/geometry 51 purple -266 141 0
simundump kpool /kinetics/CaMKII/CaMKII-thr286*-CaM 1 0 0 0 0 0 0 0 54 0 \
/kinetics/geometry 47 purple -270 141 0
simundump kpool /kinetics/CaMKII/CaMKII*** 1 0 0 0 0 0 0 0 54 0 \
/kinetics/geometry cyan purple -253 141 0
simundump kreac /kinetics/CaMKII/CaMKII-bind-CaM 1 0.92592 5 "" white purple \
-254 133 0
simundump kreac /kinetics/CaMKII/CaMK-thr286-bind-CaM 1 18.522 0.1 "" white \
purple -261 133 0
simundump kpool /kinetics/CaMKII/CaMKII-thr286 1 0 0 0 0 0 0 0 54 0 \
/kinetics/geometry red purple -261 141 0
simundump kpool /kinetics/CaMKII/tot_CaM_CaMKII 1 0 0 0 0 0 0 0 54 0 \
/kinetics/geometry green purple -268 148 0
simundump kenz /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_305 1 6.3263e-11 \
6.3263e-11 3.4162e-09 3.4162e-09 54 0.0024474 24 6 0 0 "" red green "" -256 \
138 0
simundump kenz /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_286 1 2.4454e-08 \
2.4454e-08 1.3205e-06 1.3205e-06 54 0.00020395 2 0.5 0 0 "" red green "" \
-268 138 0
simundump kpool /kinetics/CaMKII/tot_autonomous_CaMKII 1 0 2 2 108 108 0 0 54 \
0 /kinetics/geometry green purple -257 148 0
simundump kenz /kinetics/CaMKII/tot_autonomous_CaMKII/auton_305 1 4.9006e-08 \
4.9006e-08 2.6463e-06 2.6463e-06 54 0.0015873 24 6 0 0 "" red green "" -256 \
136 0
simundump kenz /kinetics/CaMKII/tot_autonomous_CaMKII/auton_286 1 1.8944e-05 \
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136 0
simundump kpool /kinetics/CaMKII/CaMK-thr305 1 0 0 0 0 0 0 0 54 0 \
/kinetics/geometry palegreen purple -247 141 0
simundump group /kinetics/CaM 1 blue black x 0 0 "" defaultfile defaultfile.g \
0 0 0 -277 112 0
simundump kpool /kinetics/CaM/CaM 1 0 26.333 26.333 1422 1422 0 0 54 0 \
/kinetics/geometry pink blue -279 124 0
simundump kreac /kinetics/CaM/CaM-TR2-bind-Ca 1 0.024691 72 "" white blue \
-275 122 0
simundump kreac /kinetics/CaM/CaM-TR2-Ca2-bind-Ca 1 0.066667 10 "" white blue \
-275 116 0
simundump kpool /kinetics/CaM/CaM-PSD 1 0 26.333 26.333 158 158 0 0 6 0 \
/kinetics/geometry[1] pink blue -316 182 0
simundump kreac /kinetics/CaM/CaM-TR2-bind-Ca-PSD 1 2 72 "" white blue -304 \
180 0
simundump kreac /kinetics/CaM/CaM-TR2-Ca2-bind-Ca-PSD 1 0.6 10 "" white blue \
-304 174 0
simundump kreac /kinetics/CaM/CaM-Ca3-bind-Ca-PSD 1 0.077502 10 "" white blue \
-304 167 0
simundump kpool /kinetics/CaM-Ca3 1 0 0 0 0 0 0 0 54 0 /kinetics/geometry \
hotpink yellow -269 113 0
simundump kpool /kinetics/CaM-TR2-Ca2 1 0 0 0 0 0 0 0 54 0 /kinetics/geometry \
pink yellow -269 119 0
simundump group /kinetics/PP1 1 yellow black x 0 0 "" defaultfile \
defaultfile.g 0 0 0 -266 95 0
simundump kpool /kinetics/PP1/I1 1 0 1.8 1.8 97.2 97.2 0 0 54 0 \
/kinetics/geometry orange yellow -257.65 90.884 0
simundump kpool /kinetics/PP1/I1* 1 0 0 0 0 0 0 0 54 0 /kinetics/geometry \
orange yellow -261.8 90.916 0
simundump kreac /kinetics/PP1/Inact-PP1 1 9.2589 0.1 "" white yellow -265.04 \
92.818 0
simundump kpool /kinetics/PP1/PP1-I1* 1 0 0 0 0 0 0 0 54 0 /kinetics/geometry \
brown yellow -263.39 96.271 0
simundump kpool /kinetics/PP1/PP1-I1 1 0 0 0 0 0 0 0 54 0 /kinetics/geometry \
brown yellow -255.98 96.547 0
simundump kreac /kinetics/PP1/dissoc-PP1-I1 1 1 0 "" white yellow -262.14 \
93.094 0
simundump kpool /kinetics/PP2A 1 0 0.11111 0.11111 6 6 0 0 54 0 \
/kinetics/geometry red black -261 107 0
simundump kenz /kinetics/PP2A/PP2A-dephosph-I1 1 1.9933e-06 1.9933e-06 \
0.00010764 0.00010764 54 0.01196 8.3334 2 0 0 "" red red "" -263.43 99.969 \
0
simundump kenz /kinetics/PP2A/PP2A-dephosph-PP1-I* 1 0.00691 0.00691 0.37314 \
0.37314 54 0.01196 8.3334 2 0 0 "" red red "" -261 105.86 0
simundump kenz /kinetics/PP2A/PP2A-dephosph-I1_PSD 1 2.2155e-07 2.2155e-07 \
1.1964e-05 1.1964e-05 54.001 0.01196 8.3334 2 0 0 "" red red "" -304 132 0
simundump kenz /kinetics/PP2A/PP2A-dephosph-PP1-I*_PSD 1 0.0012791 0.0012791 \
0.06907 0.06907 54.001 0.01196 8.3334 2 0 0 "" red red "" -304 154 0
simundump kpool /kinetics/CaNAB-Ca4 1 0 0 0 0 0 0 0 54 0 /kinetics/geometry \
tan yellow -231.92 112.43 0
simundump kenz /kinetics/CaNAB-Ca4/dephosph_inhib1_noCaM 1 0 0 0 0 54 \
0.00063333 0.136 0.034 0 0 "" red tan "" -242.54 110.5 0
simundump kenz /kinetics/CaNAB-Ca4/dephosph_inhib1_noCaM_PSD 1 0 0 0 0 54.001 \
0.00063334 0.136 0.034 0 0 "" red tan "" -304 147 0
simundump group /kinetics/PP2B 1 red3 black x 0 0 "" defaultfile \
defaultfile.g 0 0 0 -227.05 115.15 0
simundump kpool /kinetics/PP2B/CaNAB 1 0 1 1 54 54 0 0 54 0 \
/kinetics/geometry tan red3 -225.7 112.55 0
simundump kpool /kinetics/PP2B/CaNAB-Ca2 1 0 0 0 0 0 0 0 54 0 \
/kinetics/geometry tan red3 -228.26 112.46 0
simundump kreac /kinetics/PP2B/Ca-bind-CaNAB-Ca2 1 0.0012346 1 "" white red3 \
-229.83 111.25 0
simundump kreac /kinetics/PP2B/Ca-bind-CaNAB 1 3.4321 1 "" white red3 -227.12 \
111.11 0
simundump kreac /kinetics/PP2B/CaMCa4-bind-CaNAB 1 11.111 1 "" white red3 \
-234.64 113.36 0
simundump kpool /kinetics/CaMKII-thr286-CaM-PSD 0 0 0 0 0 0 0 0 6 0 \
/kinetics/geometry[1] 47 black -274 168 0
simundump kpool /kinetics/CaMKII-CaM-PSD 0 0 0 0 0 0 0 0 6 0 \
/kinetics/geometry[1] 50 black -267 168 0
simundump kpool /kinetics/CaMKII-thr286-PSD 0 0 0 0 0 0 0 0 6 0 \
/kinetics/geometry[1] 57 black -261 168 0
simundump kpool /kinetics/CaMKII-PSD 0 0 0 0 0 0 0 0 6 0 \
/kinetics/geometry[1] 62 black -255 168 0
simundump kpool /kinetics/CaMKII***-PSD 0 0 0 0 0 0 0 0 6 0 \
/kinetics/geometry[1] 0 black -249 168 0
simundump kpool /kinetics/tot-auto-PSD 0 0 2 2 12 12 0 0 6 0 \
/kinetics/geometry[1] 29 black -252 176 0
simundump kenz /kinetics/tot-auto-PSD/auton-305-PSD 0 0 0 0 0 54.001 0.01 24 \
6 0 0 "" red 29 "" -251 161 0
simundump kenz /kinetics/tot-auto-PSD/auton-286-PSD 0 0 0 0 0 7.732 \
0.00083333 2 0.5 0 0 "" red 29 "" -269 162 0
simundump kenz /kinetics/tot-auto-PSD/auton-autoph 0 0 0 0 0 7.732 0.0033333 \
8 2 0 0 "" red 29 "" -260 162 0
simundump kreac /kinetics/CaMKII-bind-CaM-PSD 0 8.3333 0 "" white black -265 \
174 0
simundump kreac /kinetics/transloc_1 0 2e-05 0 "" white black -267 158 0
simundump kreac /kinetics/transloc_2 0 2e-05 0 "" white black -274 158 0
simundump kreac /kinetics/back_1 0 0.3 1e-05 "" white black -255 158 0
simundump kreac /kinetics/back_2 0 0.3 1e-05 "" white black -241 159 0
simundump kreac /kinetics/CaMKII-thr286-bind-CaM-PSD 0 166.67 0.1 "" white \
black -276 174 0
simundump kpool /kinetics/CaM-TR2-Ca2-PSD 1 0 0 0 0 0 0 0 6 0 \
/kinetics/geometry[1] pink yellow -299 177 0
simundump kpool /kinetics/CaM-Ca3-PSD 1 0 0.0025458 0.0025458 0.015275 \
0.015275 0 0 6 0 /kinetics/geometry[1] hotpink yellow -298 171 0
simundump kpool /kinetics/CaM-Ca4-PSD 1 0 0 0 0 0 0 0 6 0 \
/kinetics/geometry[1] blue yellow -298 163 0
simundump kpool /kinetics/Ca-PSD 0 0 0.08 0.08 0.48 0.48 0 0 6 0 \
/kinetics/geometry[1] 58 black -317 174 0
simundump kpool /kinetics/286P-PSD 0 0 0 0 0 0 0 0 6 0 /kinetics/geometry[1] \
59 black -270 186 0
simundump kpool /kinetics/actCaMKII-PSD 0 0 2 2 12 12 0 0 6 0 \
/kinetics/geometry[1] 12 black -261 184 0
simundump kpool /kinetics/tot_CaMKII_PSD 0 0 2 2 12 12 0 0 6 0 \
/kinetics/geometry[1] 23 black -252 186 0
simundump kpool /kinetics/tot_CaMKII_cyt 0 0 22 22 1188 1188 0 0 54 0 \
/kinetics/geometry 24 black -252 152 0
simundump kreac /kinetics/equilib 0 540 60 "" white black -280 135 0
simundump group /kinetics/PP1_PSD 1 yellow black x 0 0 "" PP1_PSD \
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simundump kpool /kinetics/PP1_PSD/I1 1 0 4 4 24 24 0 0 6 0 \
/kinetics/geometry[1] orange yellow -301.65 140.88 0
simundump kpool /kinetics/PP1_PSD/I1* 1 0 0 0 0 0 0 0 6 0 \
/kinetics/geometry[1] orange yellow -307 141 0
simundump kpool /kinetics/PP1_PSD/PP1-I1* 1 0 0 0 0 0 0 0 6 0 \
/kinetics/geometry[1] brown yellow -307 148 0
simundump kpool /kinetics/PP1_PSD/PP1-I1 1 0 0 0 0 0 0 0 6 0 \
/kinetics/geometry[1] brown yellow -301 148 0
simundump kreac /kinetics/PP1_PSD/dissoc-PP1-I1 1 1 0 "" white yellow -296 \
143 0
simundump kreac /kinetics/Inact-PP1 1 83.33 0.1 "" white yellow -311 143 0
simundump kpool /kinetics/PP1-active_PSD 1 0 4 4 24 24 0 0 6 0 \
/kinetics/geometry[1] cyan yellow -305 158 0
simundump kenz /kinetics/PP1-active_PSD/Deph-thr286 0 0 0 0 0 54.001 0.083333 \
0.8 0.2 0 0 "" red cyan "" -272 171 0
simundump kenz /kinetics/PP1-active_PSD/Deph-thr286b 0 0 0 0 0 54.001 \
0.083333 0.8 0.2 0 0 "" red cyan "" -259 171 0
simundump kenz /kinetics/PP1-active_PSD/Deph-thr286c 0 0 0 0 0 54.001 \
0.083333 0.8 0.2 0 0 "" red cyan "" -245 171 0
simundump kenz /kinetics/PP1-active_PSD/Deph-thr305a 0 0 0 0 0 54.001 \
0.083333 0.8 0.2 0 0 "" red cyan "" -250 171 0
simundump kenz /kinetics/PP1-active_PSD/Deph-thr305 0 0 0 0 0 54.001 0.083333 \
0.8 0.2 0 0 "" red cyan "" -255 171 0
simundump kreac /kinetics/CaM-Ca3-bind-Ca 1 0.0086111 10 "" white yellow -274 \
111 0
simundump kpool /kinetics/act_CaMKII_cyt 0 0 2 2 108 108 0 0 54 0 \
/kinetics/geometry 14 black -262 150 0
simundump kpool /kinetics/NMDAR 0 0 120 120 720 720 0 0 6 0 \
/kinetics/geometry[1] blue black -282 153 0
simundump kreac /kinetics/CaMKII-diss-CaM 0 5 0 "" white black -258 174 0
simundump kpool /kinetics/CaM_Ca_n-CaNAB 1 0 0 0 0 0 0 0 54 0 \
/kinetics/geometry 1 yellow -237.52 114.35 0
simundump kenz /kinetics/CaM_Ca_n-CaNAB/dephosph_inhib1 1 0 0 0 0 54 \
0.0063333 1.36 0.34 0 0 "" red 1 "" -249.74 103.64 0
simundump kenz /kinetics/CaM_Ca_n-CaNAB/dephosph-PP1-I* 1 0 0 0 0 54 \
0.0063333 1.36 0.34 0 0 "" white 1 "" -254 107 0
simundump kenz /kinetics/CaM_Ca_n-CaNAB/dephosph_inhib1_PSD 1 0 0 0 0 54.001 \
0.0063334 1.36 0.34 0 0 "" red 1 "" -304 135 0
simundump kenz /kinetics/CaM_Ca_n-CaNAB/dephosph-PP1-I*_PSD 1 0 0 0 0 54.001 \
0.0063334 1.36 0.34 0 0 "" white 1 "" -304 151 0
simundump kpool /kinetics/basal_CaMKII_cyt 0 0 2 2 108 108 0 0 54 4 \
/kinetics/geometry blue black -260 154 0
simundump kpool /kinetics/basal_CaMKII_PSD 0 0 2 2 12 12 0 0 6 0 \
/kinetics/geometry[1] blue black -245 183 0
simundump kpool /kinetics/Ca_control_cyt 0 0 0.08 0.08 4.32 4.32 0 0 54 4 \
/kinetics/geometry 60 black -227 131 0
simundump kreac /kinetics/Ca_stoch_cyt 0 100 100 "" white black -229 124 0
simundump kpool /kinetics/Ca_control_PSD 0 0 0.08 0.08 0.48 0.48 0 0 6 4 \
/kinetics/geometry[1] 60 black -343 165 0
simundump kreac /kinetics/Ca_stoch_PSD 0 100 100 "" white black -333 173 0
simundump kpool /kinetics/basal_CaMKII_PSD_control 0 0 2 2 12 12 0 0 6 4 \
/kinetics/geometry[1] 59 black -232 179 0
simundump kreac /kinetics/Stoch_Basal_CaMKII_PSD 0 1 1 "" white black -235 \
187 0
simundump kpool /kinetics/tot-CaM-CaMKII-PSD 0 0 0 0 0 0 0 0 6 0 \
/kinetics/geometry[1] 47 black -269 179 0
simundump kenz /kinetics/tot-CaM-CaMKII-PSD/CaM-act-305-PSD 0 0 0 0 0 54.001 \
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simundump kenz /kinetics/tot-CaM-CaMKII-PSD/CaM-act-286-PSD 0 0 0 0 0 7.732 \
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simundump kenz /kinetics/tot-CaM-CaMKII-PSD/CaM_act_autoph 0 0 0 0 0 7.732 \
0.0052083 8 2 0 0 "" red 47 "" -261 165 0
simundump kpool /kinetics/CaMKII-thr305-PSD 0 0 0 0 0 0 0 0 6 0 \
/kinetics/geometry[1] 30 black -242 168 0
simundump doqcsinfo /kinetics/doqcsinfo 0 model3_noPKA_db.g \
CaMKII_noPKA_model3 network "Upinder S. Bhalla, NCBS" \
"Arnold Hayer and Upinder S. Bhalla, NCBS" \
"Hayer and Bhalla, PLoS Comput Biol, 2005." "General Mammalian" Neuronal \
"Synaptic Spine, Postsynaptic Density" \
"Quantitative match to experiments, Qualitative" \
"Hayer A, Bhalla US PLoS Comput Biol. 2005 Jul;1(2):137-54. Epub 2005 Jul 29. ( Peer-reviewed publication )" "Exact GENESIS implementation" \
"Replicates original data , Approximates original data " show_dumpdb
simundump xgraph /graphs/conc1 0 0 1800 0 120 0
simundump xgraph /graphs/conc2 0 0 1800 0 25 0
simundump xplot /graphs/conc1/actCaMKII-PSD.Co 3 524288 \
"delete_plot.w ; edit_plot.D " 12 0 0 1
simundump xplot /graphs/conc1/tot_CaMKII_PSD.Co 3 524288 \
"delete_plot.w ; edit_plot.D " 23 0 0 1
simundump xplot /graphs/conc1/act_CaMKII_cyt.Co 3 524288 \
"delete_plot.w ; edit_plot.D " 14 0 0 1
simundump xplot /graphs/conc1/tot_CaMKII_cyt.Co 3 524288 \
"delete_plot.w ; edit_plot.D " 24 0 0 1
simundump xplot /graphs/conc1/CaM_Ca_n-CaNAB.Co 3 524288 \
"delete_plot.w ; edit_plot.D " 1 0 0 1
simundump xplot /graphs/conc2/CaM-Ca4-PSD.Co 3 524288 \
"delete_plot.w ; edit_plot.D " blue 0 0 1
simundump xgraph /moregraphs/conc3 0 0 1800 0 0.1 0
simundump xgraph /moregraphs/conc4 0 0 1800 0 5.1622 0
simundump xplot /moregraphs/conc3/PP1-active_PSD.Co 3 524288 \
"delete_plot.w ; edit_plot.D " cyan 0 0 1
simundump xplot /moregraphs/conc3/PKA-active.Co 3 524288 \
"delete_plot.w ; edit_plot.D " yellow 0 0 1
simundump xplot /moregraphs/conc3/Ca.Co 3 524288 \
"delete_plot.w ; edit_plot.D " red 0 0 1
simundump xplot /moregraphs/conc4/PP1-active.Co 3 524288 \
"delete_plot.w ; edit_plot.D " cyan 0 0 1
simundump xplot /moregraphs/conc4/CaM-Ca4.Co 3 524288 \
"delete_plot.w ; edit_plot.D " blue 0 0 1
simundump xcoredraw /edit/draw 0 -345 -207 87.744 189
simundump xtree /edit/draw/tree 0 \
/kinetics/#[],/kinetics/#[]/#[],/kinetics/#[]/#[]/#[][TYPE!=proto],/kinetics/#[]/#[]/#[][TYPE!=linkinfo]/##[] \
"edit_elm.D ; drag_from_edit.w " auto 0.6
simundump xtext /file/notes 0 1
xtextload /file/notes \
"16 June 2004. Based on revised version of Arnolds model dated" \
"around 10 June. Setting up for stoch runs controlling enzyme levels." \
"- Removed MAPK and other pathways that have no effect due to" \
"buffering of downstream outputs." \
"- Added PKC control" \
"- Added Ca control for cyt and PSD" \
"- Altered init levels for PKA while keeping total amount fixed," \
" in order to provide a wider range for altering starting levels" \
" of R2-cAMP4." \
"- Added a few plots, notably of these signaling molecules." \
"" \
"18 June 2004. Added stoch reaction control of Basal_CaMKII_PSD" \
"" \
"29 June 2004. Added elements for turnover: the turnover control," \
" and the anchor. Also several plots." \
"" \
"1 July 2004. Fine-tuning the turnover model to fit experimental" \
" constraints. exo_reg is now at kf=3e-5 from 1.5e-5," \
" because the amount" \
" of Anchor is scaled down to 100 from 200. Also added a plot" \
" for the molecule being contacted for recycling, AMPAR/A12_B12." \
" Saved as model_1c_equil_turnover.g" \
"" \
"5 July 2004. Fixed two issues with the model_1c_equil_turnover.g:" \
" - Outright bug: The Ca_control_PSD had a volume of 9e-20," \
" so all its conc scalings were wrong. Fixed to 1e-20." \
" - Activated CaN (PP2B, pool name CaM_Ca_n-CaNAB) was a sumtotal." \
" As a key part of our discussion is the presence of substrate" \
" saturation of phosphatases, this is a problem. I replaced" \
" it with a single activation reaction using Ca4.CaM." \
"Saved as model_1d_equil_turnover.g" \
"" \
"6 July 2004." \
" Based on model_1d_equil_turnover.g. Three changes:" \
" - Set the turnover rate for AMPA_bulk to and from A12_B12" \
" to kf = kb = 1." \
" - Fixed the volume terms for some of the internal AMPA" \
" pools, which had been erroneously set to the PSD volume." \
" As all calculations are in terms of n, this is a cosmetic" \
" fix." \
" - Set up conditions so that the simulation would settle to" \
" baseline (low) activity. Ran, and saved the model in this" \
" low activity state." \
"Saved as model_1e_equil_turnover.g" \
"" \
"6 July 2004. Shifted anchor from handling just the membrane-" \
" inserted receptor, to handling the entire spine allowance" \
" of AMPAR. Restored the exo_reg[0-3] rates to the original" \
" 0.0015/sec. Changed the turnover forward reacn to 0.01." \
"Saved as model_1f_equil_turnover.g" \
"" \
"9 July 2004. Added plot for CaM_Ca_n-CaNAB, same name." \
"" \
"29 July 2004. Using PSD anchor for GluR again. Also putting in" \
"a degradation step for GluR both in internal region and" \
"in the memb, to prevent levels from building up" \
"arbitrarily. The degradation acts only on phosphorylated forms" \
"for Ser831, not the 845 site. " \
"Saved as model_1g_equil_turnover.g" \
"" \
"29 July 2004. Much more detail. Degradation now applied at" \
"Ehlers rate of 5e-5, to each AMPAR molecule. 32 reaction steps." \
"Saved as model_1h_equil_turnover.g" \
"" \
"10 Nov 2004. Cleared out all AMPAR from synapse by running at" \
"high degradation and no influx. Also set turnover kf and kb to 1." \
"Saved as model_1h_noAMPAR.g" \
"" \
"30 Nov 2004. Some further cleanups, zeroing out some of the" \
"molecules that are nearly zero." \
"Saved as transloc_nov04.g" \
"" \
"30 Nov 2004. Putting in the AMPAR parameters." \
"Saved as transloc_nov04.g" \
"" \
"1 Dec 2004. Fixing up CaMKII autophosph rates to match the work" \
"done in early Nov on CaMKII responses. Also fixed" \
"a silly naming issue with the CaM-activated CaMKII in the PSD." \
"Saved as transloc_dec04a.g" \
"" \
"1 Dec 2004. Cleaned up CaMKII initial conditions, all the CaMKII" \
"now starts up in the cytosolic pool. It will settle rapidly" \
"so this is not a problem for long runs." \
"Saved as transloc_dec04b.g" \
"" \
"1 Dec 2004. Cleaning up PKA initial conditions. Looks like there" \
"was a problem in the initial levels of PKA, nearly but not" \
"quite doubled it in the course of doing one of the equilibration" \
"runs." \
"Saved as transloc_dec04c.g" \
"" \
"1 Dec 2004. Cleaning up PP2B initial levels. Saved as" \
"transloc_dec04d.g" \
"" \
"1 Dec 2004. Cleaning up PP1 initial levels, PSD and cytosolic." \
"Saved as transloc_dec04e.g" \
"" \
"1 Dec 2004. Eliminated degradation steps for AMPAR." \
"Saved as transloc_dec04f.g" \
"" \
"2 Dec 2004. Fixed volume conversion issue with forward rate for" \
"/kinetics/AMPAR/exo_reg[]. " \
"Saved as transloc_dec04g.g" \
"" \
"15 Dec 2004. Set a backward rate of kb = 0.002" \
"for /kinetics/AMPAR/exo_reg[]" \
"so that the overall translocation rate is reasonable. " \
"Saved as transloc_dec04h.g" \
"" \
"16 Dec 2004. Working out CaMKII translocation rates to match" \
"figures from Shen and Meyer Science 1999. Saved as" \
"transloc_dec04i.g" \
"" \
"16 Dec 2004. Added autophosph step for bistability. Saved as" \
"transloc_dec04i_bis1.g" \
"" \
"17 Dec 2004. Cleaned up CaMKII translocation reactions. Eliminated" \
"bistability step. Saved as transloc_dec04j.g" \
"" \
"20 Dec 2004. Fixed mass consv error in j model, worked a little" \
"on rates to make things a little more like expt. Saved as" \
"transloc_dec04k.g" \
"" \
"21 Dec 2004. Fine-tuned to match turnon and turnoff curves." \
"Did so by lowering Km of PP1 for CaMKII, and by scaling NMDAR" \
"numbers." \
"Saved as transloc_dec04n.g. Note that there is another branch," \
"m.g, where the fine-tuning was done by varying PP1 levels." \
"" \
"17 Jan 2005. More fine-tuning, keeping traffic matched." \
"/kinetics/AMPAR/exo_reg[] kb = 0.0016" \
"/kinetics/PP1-active_PSD/PP1[] kf = 0.14583 // Km of 2" \
"/kinetics/PP1-active_PSD nInit 24 // orig was 18" \
"/kinetics/PP1_PSD/I1/nInit 24 // orig was 18" \
"Saved in transloc_dec04m.g" \
"" \
"25 Jan 2005. Fixed the level of the AMPAR-bulk to 0.6 molecules," \
"buffered. Saved as" \
"transloc_jan05a.g" \
"" \
"31 Jan 2005. Fixed exo rate: kb now 0.008, from 0.0016. Also" \
"the AMPA_bulk was 0.6, corrected to 0.5 now. Saved as" \
"transloc_jan05b.g" \
"" \
"3 Feb 2005. Fixed some silly volumes. Saved as" \
"transloc_feb05a.g" \
"" \
"4 Feb 2005. CaMKII bistability version of model. Saved as" \
"transloc_feb05a_ckbis.g" \
"" \
"4 Feb 2005. Lockstep version of model. Saved as" \
"transloc_feb05a_lockstep.g" \
"" \
"14 Feb 2005. Eliminated non-CaMKII stuff from lockstep model." \
"Saved as CaMKII_bis_only.g" \
"" \
"14 Feb 2005. Fixed PKA basal level to ninit = 1." \
"Saved as CaMKII_bis_only1.g" \
"" \
"14 Feb 2005. Finally, a bistable model. Saved as" \
"CaMKII_bis_only2.g" \
"" \
"16 Feb 2005. CaMKII_bis_only3.g. Variant where the CaMKII" \
"Kms in the PSD are all doubled, and the Vmax for PP1 is" \
"down from 0.5 to 0.4." \
"" \
"17 Feb 2005. CaMKII_bis_only6.g Based on bis_only4.g, but" \
"here I have also scaled the cytosolic CaMKII autophosph Km up" \
"2x." \
"" \
"17 Feb 2005. CaMKII_bis_only8.g Based on only6. Scaled CaMKII" \
"autophosph Km 2x more, scaled down Vmax for PP1-PSD from 0.35" \
"to 0.2 to compensate." \
"" \
"25 Feb 2005. CaMKII_bis_onlyk.g Based on only8. Fixed the " \
"problem with CaM levels, should be 26.3333 uM. Also several" \
"other fixes mostly to do with roundoff." \
"" \
"1 March 2005. CaMKII_bis_onlyk.g" \
"One thing to watch out for when merging this model is that" \
"PKA-active is set to 1 molecule, as the regulation of PKA" \
"is not modeled. Had mistakenly zeroed it out." \
"" \
"21 June 2005. CaMKII_traff.g" \
"Final version of model, minor cleanups with naming so that" \
"the thr306 is now eliminated." \
""
addmsg /kinetics/CaMKII/CaMKII-bind-CaM /kinetics/CaM-Ca4 REAC A B
addmsg /kinetics/CaMKII/CaMK-thr286-bind-CaM /kinetics/CaM-Ca4 REAC A B
addmsg /kinetics/CaM-Ca3-bind-Ca /kinetics/CaM-Ca4 REAC B A
addmsg /kinetics/PP2B/CaMCa4-bind-CaNAB /kinetics/CaM-Ca4 REAC A B
addmsg /kinetics/equilib /kinetics/CaM-Ca4 REAC B A
addmsg /kinetics/PP1/Inact-PP1 /kinetics/PP1-active REAC A B
addmsg /kinetics/PP1/dissoc-PP1-I1 /kinetics/PP1-active REAC B A
addmsg /kinetics/PP1-active/Deph-thr286 /kinetics/PP1-active REAC eA B
addmsg /kinetics/PP1-active/Deph-thr286b /kinetics/PP1-active REAC eA B
addmsg /kinetics/PP1-active/Deph-thr305 /kinetics/PP1-active REAC eA B
addmsg /kinetics/PP1-active/Deph-thr286c /kinetics/PP1-active REAC eA B
addmsg /kinetics/PP1-active/Deph-thr305a /kinetics/PP1-active REAC eA B
addmsg /kinetics/PP1-active /kinetics/PP1-active/Deph-thr286 ENZYME n
addmsg /kinetics/CaMKII/CaMKII-thr286*-CaM /kinetics/PP1-active/Deph-thr286 SUBSTRATE n
addmsg /kinetics/PP1-active /kinetics/PP1-active/Deph-thr286b ENZYME n
addmsg /kinetics/CaMKII/CaMKII-thr286 /kinetics/PP1-active/Deph-thr286b SUBSTRATE n
addmsg /kinetics/PP1-active /kinetics/PP1-active/Deph-thr305 ENZYME n
addmsg /kinetics/CaMKII/CaMKII*** /kinetics/PP1-active/Deph-thr305 SUBSTRATE n
addmsg /kinetics/PP1-active /kinetics/PP1-active/Deph-thr286c ENZYME n
addmsg /kinetics/CaMKII/CaMKII*** /kinetics/PP1-active/Deph-thr286c SUBSTRATE n
addmsg /kinetics/PP1-active /kinetics/PP1-active/Deph-thr305a ENZYME n
addmsg /kinetics/CaMKII/CaMK-thr305 /kinetics/PP1-active/Deph-thr305a SUBSTRATE n
addmsg /kinetics/CaM/CaM-TR2-bind-Ca /kinetics/Ca REAC A B
addmsg /kinetics/CaM/CaM-TR2-bind-Ca /kinetics/Ca REAC A B
addmsg /kinetics/CaM/CaM-TR2-Ca2-bind-Ca /kinetics/Ca REAC A B
addmsg /kinetics/CaM-Ca3-bind-Ca /kinetics/Ca REAC A B
addmsg /kinetics/PP2B/Ca-bind-CaNAB-Ca2 /kinetics/Ca REAC A B
addmsg /kinetics/PP2B/Ca-bind-CaNAB-Ca2 /kinetics/Ca REAC A B
addmsg /kinetics/PP2B/Ca-bind-CaNAB /kinetics/Ca REAC A B
addmsg /kinetics/PP2B/Ca-bind-CaNAB /kinetics/Ca REAC A B
addmsg /kinetics/Ca_stoch_cyt /kinetics/Ca REAC B A
addmsg /kinetics/PKA-active/PKA-phosph-I1 /kinetics/PKA-active REAC eA B
addmsg /kinetics/PKA-active/PKA-phosph-I1_PSD /kinetics/PKA-active REAC eA B
addmsg /kinetics/PKA-active /kinetics/PKA-active/PKA-phosph-I1 ENZYME n
addmsg /kinetics/PP1/I1 /kinetics/PKA-active/PKA-phosph-I1 SUBSTRATE n
addmsg /kinetics/PKA-active /kinetics/PKA-active/PKA-phosph-I1_PSD ENZYME n
addmsg /kinetics/PP1_PSD/I1 /kinetics/PKA-active/PKA-phosph-I1_PSD SUBSTRATE n
addmsg /kinetics/CaMKII/CaMKII-bind-CaM /kinetics/CaMKII/CaMKII REAC A B
addmsg /kinetics/back_1 /kinetics/CaMKII/CaMKII REAC B A
addmsg /kinetics/PP1-active/Deph-thr286b /kinetics/CaMKII/CaMKII MM_PRD pA
addmsg /kinetics/PP1-active/Deph-thr305a /kinetics/CaMKII/CaMKII MM_PRD pA
addmsg /kinetics/CaMKII/CaMKII-bind-CaM /kinetics/CaMKII/CaMKII-CaM REAC B A
addmsg /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_286 /kinetics/CaMKII/CaMKII-CaM REAC sA B
addmsg /kinetics/CaMKII/tot_autonomous_CaMKII/auton_286 /kinetics/CaMKII/CaMKII-CaM REAC sA B
addmsg /kinetics/transloc_1 /kinetics/CaMKII/CaMKII-CaM REAC A B
addmsg /kinetics/PP1-active/Deph-thr286 /kinetics/CaMKII/CaMKII-CaM MM_PRD pA
addmsg /kinetics/CaMKII/CaMK-thr286-bind-CaM /kinetics/CaMKII/CaMKII-thr286*-CaM REAC B A
addmsg /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_286 /kinetics/CaMKII/CaMKII-thr286*-CaM MM_PRD pA
addmsg /kinetics/CaMKII/tot_autonomous_CaMKII/auton_286 /kinetics/CaMKII/CaMKII-thr286*-CaM MM_PRD pA
addmsg /kinetics/transloc_2 /kinetics/CaMKII/CaMKII-thr286*-CaM REAC A B
addmsg /kinetics/PP1-active/Deph-thr286 /kinetics/CaMKII/CaMKII-thr286*-CaM REAC sA B
addmsg /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_305 /kinetics/CaMKII/CaMKII*** MM_PRD pA
addmsg /kinetics/CaMKII/tot_autonomous_CaMKII/auton_305 /kinetics/CaMKII/CaMKII*** MM_PRD pA
addmsg /kinetics/PP1-active/Deph-thr305 /kinetics/CaMKII/CaMKII*** REAC sA B
addmsg /kinetics/PP1-active/Deph-thr286c /kinetics/CaMKII/CaMKII*** REAC sA B
addmsg /kinetics/CaM-Ca4 /kinetics/CaMKII/CaMKII-bind-CaM SUBSTRATE n
addmsg /kinetics/CaMKII/CaMKII /kinetics/CaMKII/CaMKII-bind-CaM SUBSTRATE n
addmsg /kinetics/CaMKII/CaMKII-CaM /kinetics/CaMKII/CaMKII-bind-CaM PRODUCT n
addmsg /kinetics/CaMKII/CaMKII-thr286 /kinetics/CaMKII/CaMK-thr286-bind-CaM SUBSTRATE n
addmsg /kinetics/CaM-Ca4 /kinetics/CaMKII/CaMK-thr286-bind-CaM SUBSTRATE n
addmsg /kinetics/CaMKII/CaMKII-thr286*-CaM /kinetics/CaMKII/CaMK-thr286-bind-CaM PRODUCT n
addmsg /kinetics/CaMKII/CaMK-thr286-bind-CaM /kinetics/CaMKII/CaMKII-thr286 REAC A B
addmsg /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_305 /kinetics/CaMKII/CaMKII-thr286 REAC sA B
addmsg /kinetics/CaMKII/tot_autonomous_CaMKII/auton_305 /kinetics/CaMKII/CaMKII-thr286 REAC sA B
addmsg /kinetics/PP1-active/Deph-thr286b /kinetics/CaMKII/CaMKII-thr286 REAC sA B
addmsg /kinetics/PP1-active/Deph-thr305 /kinetics/CaMKII/CaMKII-thr286 MM_PRD pA
addmsg /kinetics/CaMKII/CaMKII-CaM /kinetics/CaMKII/tot_CaM_CaMKII SUMTOTAL n nInit
addmsg /kinetics/CaMKII/CaMKII-thr286*-CaM /kinetics/CaMKII/tot_CaM_CaMKII SUMTOTAL n nInit
addmsg /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_305 /kinetics/CaMKII/tot_CaM_CaMKII REAC eA B
addmsg /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_286 /kinetics/CaMKII/tot_CaM_CaMKII REAC eA B
addmsg /kinetics/CaMKII/tot_CaM_CaMKII /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_305 ENZYME n
addmsg /kinetics/CaMKII/CaMKII-thr286 /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_305 SUBSTRATE n
addmsg /kinetics/CaMKII/tot_CaM_CaMKII /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_286 ENZYME n
addmsg /kinetics/CaMKII/CaMKII-CaM /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_286 SUBSTRATE n
addmsg /kinetics/CaMKII/CaMKII-thr286 /kinetics/CaMKII/tot_autonomous_CaMKII SUMTOTAL n nInit
addmsg /kinetics/CaMKII/CaMKII*** /kinetics/CaMKII/tot_autonomous_CaMKII SUMTOTAL n nInit
addmsg /kinetics/CaMKII/tot_autonomous_CaMKII/auton_305 /kinetics/CaMKII/tot_autonomous_CaMKII REAC eA B
addmsg /kinetics/CaMKII/tot_autonomous_CaMKII/auton_286 /kinetics/CaMKII/tot_autonomous_CaMKII REAC eA B
addmsg /kinetics/basal_CaMKII_cyt /kinetics/CaMKII/tot_autonomous_CaMKII SUMTOTAL n nInit
addmsg /kinetics/CaMKII/tot_autonomous_CaMKII /kinetics/CaMKII/tot_autonomous_CaMKII/auton_305 ENZYME n
addmsg /kinetics/CaMKII/CaMKII-thr286 /kinetics/CaMKII/tot_autonomous_CaMKII/auton_305 SUBSTRATE n
addmsg /kinetics/CaMKII/tot_autonomous_CaMKII /kinetics/CaMKII/tot_autonomous_CaMKII/auton_286 ENZYME n
addmsg /kinetics/CaMKII/CaMKII-CaM /kinetics/CaMKII/tot_autonomous_CaMKII/auton_286 SUBSTRATE n
addmsg /kinetics/back_2 /kinetics/CaMKII/CaMK-thr305 REAC B A
addmsg /kinetics/PP1-active/Deph-thr305a /kinetics/CaMKII/CaMK-thr305 REAC sA B
addmsg /kinetics/PP1-active/Deph-thr286c /kinetics/CaMKII/CaMK-thr305 MM_PRD pA
addmsg /kinetics/CaM/CaM-TR2-bind-Ca /kinetics/CaM/CaM REAC A B
addmsg /kinetics/CaM/CaM /kinetics/CaM/CaM-TR2-bind-Ca SUBSTRATE n
addmsg /kinetics/CaM-TR2-Ca2 /kinetics/CaM/CaM-TR2-bind-Ca PRODUCT n
addmsg /kinetics/Ca /kinetics/CaM/CaM-TR2-bind-Ca SUBSTRATE n
addmsg /kinetics/Ca /kinetics/CaM/CaM-TR2-bind-Ca SUBSTRATE n
addmsg /kinetics/CaM-TR2-Ca2 /kinetics/CaM/CaM-TR2-Ca2-bind-Ca SUBSTRATE n
addmsg /kinetics/Ca /kinetics/CaM/CaM-TR2-Ca2-bind-Ca SUBSTRATE n
addmsg /kinetics/CaM-Ca3 /kinetics/CaM/CaM-TR2-Ca2-bind-Ca PRODUCT n
addmsg /kinetics/CaM/CaM-TR2-bind-Ca-PSD /kinetics/CaM/CaM-PSD REAC A B
addmsg /kinetics/CaM/CaM-PSD /kinetics/CaM/CaM-TR2-bind-Ca-PSD SUBSTRATE n
addmsg /kinetics/CaM-TR2-Ca2-PSD /kinetics/CaM/CaM-TR2-bind-Ca-PSD PRODUCT n
addmsg /kinetics/Ca-PSD /kinetics/CaM/CaM-TR2-bind-Ca-PSD SUBSTRATE n
addmsg /kinetics/Ca-PSD /kinetics/CaM/CaM-TR2-bind-Ca-PSD SUBSTRATE n
addmsg /kinetics/CaM-TR2-Ca2-PSD /kinetics/CaM/CaM-TR2-Ca2-bind-Ca-PSD SUBSTRATE n
addmsg /kinetics/CaM-Ca3-PSD /kinetics/CaM/CaM-TR2-Ca2-bind-Ca-PSD PRODUCT n
addmsg /kinetics/Ca-PSD /kinetics/CaM/CaM-TR2-Ca2-bind-Ca-PSD SUBSTRATE n
addmsg /kinetics/CaM-Ca3-PSD /kinetics/CaM/CaM-Ca3-bind-Ca-PSD SUBSTRATE n
addmsg /kinetics/CaM-Ca4-PSD /kinetics/CaM/CaM-Ca3-bind-Ca-PSD PRODUCT n
addmsg /kinetics/Ca-PSD /kinetics/CaM/CaM-Ca3-bind-Ca-PSD SUBSTRATE n
addmsg /kinetics/CaM/CaM-TR2-Ca2-bind-Ca /kinetics/CaM-Ca3 REAC B A
addmsg /kinetics/CaM-Ca3-bind-Ca /kinetics/CaM-Ca3 REAC A B
addmsg /kinetics/CaM/CaM-TR2-bind-Ca /kinetics/CaM-TR2-Ca2 REAC B A
addmsg /kinetics/CaM/CaM-TR2-Ca2-bind-Ca /kinetics/CaM-TR2-Ca2 REAC A B
addmsg /kinetics/CaNAB-Ca4/dephosph_inhib1_noCaM /kinetics/PP1/I1 MM_PRD pA
addmsg /kinetics/CaM_Ca_n-CaNAB/dephosph_inhib1 /kinetics/PP1/I1 MM_PRD pA
addmsg /kinetics/PP2A/PP2A-dephosph-I1 /kinetics/PP1/I1 MM_PRD pA
addmsg /kinetics/PP1/dissoc-PP1-I1 /kinetics/PP1/I1 REAC B A
addmsg /kinetics/PKA-active/PKA-phosph-I1 /kinetics/PP1/I1 REAC sA B
addmsg /kinetics/PP1/Inact-PP1 /kinetics/PP1/I1* REAC A B
addmsg /kinetics/CaNAB-Ca4/dephosph_inhib1_noCaM /kinetics/PP1/I1* REAC sA B
addmsg /kinetics/CaM_Ca_n-CaNAB/dephosph_inhib1 /kinetics/PP1/I1* REAC sA B
addmsg /kinetics/PP2A/PP2A-dephosph-I1 /kinetics/PP1/I1* REAC sA B
addmsg /kinetics/PKA-active/PKA-phosph-I1 /kinetics/PP1/I1* MM_PRD pA
addmsg /kinetics/PP1/PP1-I1* /kinetics/PP1/Inact-PP1 PRODUCT n
addmsg /kinetics/PP1/I1* /kinetics/PP1/Inact-PP1 SUBSTRATE n
addmsg /kinetics/PP1-active /kinetics/PP1/Inact-PP1 SUBSTRATE n
addmsg /kinetics/PP1/Inact-PP1 /kinetics/PP1/PP1-I1* REAC B A
addmsg /kinetics/PP2A/PP2A-dephosph-PP1-I* /kinetics/PP1/PP1-I1* REAC sA B
addmsg /kinetics/CaM_Ca_n-CaNAB/dephosph-PP1-I* /kinetics/PP1/PP1-I1* REAC sA B
addmsg /kinetics/PP1/dissoc-PP1-I1 /kinetics/PP1/PP1-I1 REAC A B
addmsg /kinetics/PP2A/PP2A-dephosph-PP1-I* /kinetics/PP1/PP1-I1 MM_PRD pA
addmsg /kinetics/CaM_Ca_n-CaNAB/dephosph-PP1-I* /kinetics/PP1/PP1-I1 MM_PRD pA
addmsg /kinetics/PP1/PP1-I1 /kinetics/PP1/dissoc-PP1-I1 SUBSTRATE n
addmsg /kinetics/PP1-active /kinetics/PP1/dissoc-PP1-I1 PRODUCT n
addmsg /kinetics/PP1/I1 /kinetics/PP1/dissoc-PP1-I1 PRODUCT n
addmsg /kinetics/PP2A/PP2A-dephosph-I1 /kinetics/PP2A REAC eA B
addmsg /kinetics/PP2A/PP2A-dephosph-PP1-I* /kinetics/PP2A REAC eA B
addmsg /kinetics/PP2A/PP2A-dephosph-I1_PSD /kinetics/PP2A REAC eA B
addmsg /kinetics/PP2A/PP2A-dephosph-PP1-I*_PSD /kinetics/PP2A REAC eA B
addmsg /kinetics/PP2A /kinetics/PP2A/PP2A-dephosph-I1 ENZYME n
addmsg /kinetics/PP1/I1* /kinetics/PP2A/PP2A-dephosph-I1 SUBSTRATE n
addmsg /kinetics/PP2A /kinetics/PP2A/PP2A-dephosph-PP1-I* ENZYME n
addmsg /kinetics/PP1/PP1-I1* /kinetics/PP2A/PP2A-dephosph-PP1-I* SUBSTRATE n
addmsg /kinetics/PP2A /kinetics/PP2A/PP2A-dephosph-I1_PSD ENZYME n
addmsg /kinetics/PP1_PSD/I1* /kinetics/PP2A/PP2A-dephosph-I1_PSD SUBSTRATE n
addmsg /kinetics/PP2A /kinetics/PP2A/PP2A-dephosph-PP1-I*_PSD ENZYME n
addmsg /kinetics/PP1_PSD/PP1-I1* /kinetics/PP2A/PP2A-dephosph-PP1-I*_PSD SUBSTRATE n
addmsg /kinetics/CaNAB-Ca4/dephosph_inhib1_noCaM /kinetics/CaNAB-Ca4 REAC eA B
addmsg /kinetics/PP2B/Ca-bind-CaNAB-Ca2 /kinetics/CaNAB-Ca4 REAC B A
addmsg /kinetics/PP2B/CaMCa4-bind-CaNAB /kinetics/CaNAB-Ca4 REAC A B
addmsg /kinetics/CaNAB-Ca4/dephosph_inhib1_noCaM_PSD /kinetics/CaNAB-Ca4 REAC eA B
addmsg /kinetics/CaNAB-Ca4 /kinetics/CaNAB-Ca4/dephosph_inhib1_noCaM ENZYME n
addmsg /kinetics/PP1/I1* /kinetics/CaNAB-Ca4/dephosph_inhib1_noCaM SUBSTRATE n
addmsg /kinetics/CaNAB-Ca4 /kinetics/CaNAB-Ca4/dephosph_inhib1_noCaM_PSD ENZYME n
addmsg /kinetics/PP1_PSD/I1* /kinetics/CaNAB-Ca4/dephosph_inhib1_noCaM_PSD SUBSTRATE n
addmsg /kinetics/PP2B/Ca-bind-CaNAB /kinetics/PP2B/CaNAB REAC A B
addmsg /kinetics/PP2B/Ca-bind-CaNAB /kinetics/PP2B/CaNAB-Ca2 REAC B A
addmsg /kinetics/PP2B/Ca-bind-CaNAB-Ca2 /kinetics/PP2B/CaNAB-Ca2 REAC A B
addmsg /kinetics/CaNAB-Ca4 /kinetics/PP2B/Ca-bind-CaNAB-Ca2 PRODUCT n
addmsg /kinetics/Ca /kinetics/PP2B/Ca-bind-CaNAB-Ca2 SUBSTRATE n
addmsg /kinetics/Ca /kinetics/PP2B/Ca-bind-CaNAB-Ca2 SUBSTRATE n
addmsg /kinetics/PP2B/CaNAB-Ca2 /kinetics/PP2B/Ca-bind-CaNAB-Ca2 SUBSTRATE n
addmsg /kinetics/PP2B/CaNAB /kinetics/PP2B/Ca-bind-CaNAB SUBSTRATE n
addmsg /kinetics/PP2B/CaNAB-Ca2 /kinetics/PP2B/Ca-bind-CaNAB PRODUCT n
addmsg /kinetics/Ca /kinetics/PP2B/Ca-bind-CaNAB SUBSTRATE n
addmsg /kinetics/Ca /kinetics/PP2B/Ca-bind-CaNAB SUBSTRATE n
addmsg /kinetics/CaM-Ca4 /kinetics/PP2B/CaMCa4-bind-CaNAB SUBSTRATE n
addmsg /kinetics/CaNAB-Ca4 /kinetics/PP2B/CaMCa4-bind-CaNAB SUBSTRATE n
addmsg /kinetics/CaM_Ca_n-CaNAB /kinetics/PP2B/CaMCa4-bind-CaNAB PRODUCT n
addmsg /kinetics/transloc_2 /kinetics/CaMKII-thr286-CaM-PSD REAC B A
addmsg /kinetics/CaMKII-thr286-bind-CaM-PSD /kinetics/CaMKII-thr286-CaM-PSD REAC B A
addmsg /kinetics/tot-CaM-CaMKII-PSD/CaM-act-286-PSD /kinetics/CaMKII-thr286-CaM-PSD MM_PRD pA
addmsg /kinetics/tot-auto-PSD/auton-286-PSD /kinetics/CaMKII-thr286-CaM-PSD MM_PRD pA
addmsg /kinetics/PP1-active_PSD/Deph-thr286 /kinetics/CaMKII-thr286-CaM-PSD REAC sA B
addmsg /kinetics/transloc_1 /kinetics/CaMKII-CaM-PSD REAC B A
addmsg /kinetics/tot-CaM-CaMKII-PSD/CaM-act-286-PSD /kinetics/CaMKII-CaM-PSD REAC sA B
addmsg /kinetics/tot-auto-PSD/auton-286-PSD /kinetics/CaMKII-CaM-PSD REAC sA B
addmsg /kinetics/PP1-active_PSD/Deph-thr286 /kinetics/CaMKII-CaM-PSD MM_PRD pA
addmsg /kinetics/CaMKII-diss-CaM /kinetics/CaMKII-CaM-PSD REAC A B
addmsg /kinetics/CaMKII-bind-CaM-PSD /kinetics/CaMKII-CaM-PSD REAC B A
addmsg /kinetics/tot-CaM-CaMKII-PSD/CaM-act-305-PSD /kinetics/CaMKII-thr286-PSD REAC sA B
addmsg /kinetics/tot-auto-PSD/auton-305-PSD /kinetics/CaMKII-thr286-PSD REAC sA B
addmsg /kinetics/CaMKII-thr286-bind-CaM-PSD /kinetics/CaMKII-thr286-PSD REAC A B
addmsg /kinetics/PP1-active_PSD/Deph-thr286b /kinetics/CaMKII-thr286-PSD REAC sA B
addmsg /kinetics/PP1-active_PSD/Deph-thr305 /kinetics/CaMKII-thr286-PSD MM_PRD pA
addmsg /kinetics/tot-CaM-CaMKII-PSD/CaM_act_autoph /kinetics/CaMKII-thr286-PSD MM_PRD pA
addmsg /kinetics/tot-auto-PSD/auton-autoph /kinetics/CaMKII-thr286-PSD MM_PRD pA
addmsg /kinetics/back_1 /kinetics/CaMKII-PSD REAC A B
addmsg /kinetics/CaMKII-bind-CaM-PSD /kinetics/CaMKII-PSD REAC A B
addmsg /kinetics/PP1-active_PSD/Deph-thr305a /kinetics/CaMKII-PSD MM_PRD pA
addmsg /kinetics/PP1-active_PSD/Deph-thr286b /kinetics/CaMKII-PSD MM_PRD pA
addmsg /kinetics/CaMKII-diss-CaM /kinetics/CaMKII-PSD REAC B A
addmsg /kinetics/tot-CaM-CaMKII-PSD/CaM_act_autoph /kinetics/CaMKII-PSD REAC sA B
addmsg /kinetics/tot-auto-PSD/auton-autoph /kinetics/CaMKII-PSD REAC sA B
addmsg /kinetics/tot-CaM-CaMKII-PSD/CaM-act-305-PSD /kinetics/CaMKII***-PSD MM_PRD pA
addmsg /kinetics/tot-auto-PSD/auton-305-PSD /kinetics/CaMKII***-PSD MM_PRD pA
addmsg /kinetics/PP1-active_PSD/Deph-thr305 /kinetics/CaMKII***-PSD REAC sA B
addmsg /kinetics/PP1-active_PSD/Deph-thr286c /kinetics/CaMKII***-PSD REAC sA B
addmsg /kinetics/CaMKII-thr286-PSD /kinetics/tot-auto-PSD SUMTOTAL n nInit
addmsg /kinetics/CaMKII***-PSD /kinetics/tot-auto-PSD SUMTOTAL n nInit
addmsg /kinetics/tot-auto-PSD/auton-305-PSD /kinetics/tot-auto-PSD REAC eA B
addmsg /kinetics/tot-auto-PSD/auton-286-PSD /kinetics/tot-auto-PSD REAC eA B
addmsg /kinetics/basal_CaMKII_PSD /kinetics/tot-auto-PSD SUMTOTAL n nInit
addmsg /kinetics/tot-auto-PSD/auton-autoph /kinetics/tot-auto-PSD REAC eA B
addmsg /kinetics/tot-auto-PSD /kinetics/tot-auto-PSD/auton-305-PSD ENZYME n
addmsg /kinetics/CaMKII-thr286-PSD /kinetics/tot-auto-PSD/auton-305-PSD SUBSTRATE n
addmsg /kinetics/tot-auto-PSD /kinetics/tot-auto-PSD/auton-286-PSD ENZYME n
addmsg /kinetics/CaMKII-CaM-PSD /kinetics/tot-auto-PSD/auton-286-PSD SUBSTRATE n
addmsg /kinetics/tot-auto-PSD /kinetics/tot-auto-PSD/auton-autoph ENZYME n
addmsg /kinetics/CaMKII-PSD /kinetics/tot-auto-PSD/auton-autoph SUBSTRATE n
addmsg /kinetics/CaMKII-PSD /kinetics/CaMKII-bind-CaM-PSD SUBSTRATE n
addmsg /kinetics/CaM-Ca4-PSD /kinetics/CaMKII-bind-CaM-PSD SUBSTRATE n
addmsg /kinetics/CaMKII-CaM-PSD /kinetics/CaMKII-bind-CaM-PSD PRODUCT n
addmsg /kinetics/CaMKII/CaMKII-CaM /kinetics/transloc_1 SUBSTRATE n
addmsg /kinetics/CaMKII-CaM-PSD /kinetics/transloc_1 PRODUCT n
addmsg /kinetics/NMDAR /kinetics/transloc_1 SUBSTRATE n
addmsg /kinetics/CaMKII/CaMKII-thr286*-CaM /kinetics/transloc_2 SUBSTRATE n
addmsg /kinetics/CaMKII-thr286-CaM-PSD /kinetics/transloc_2 PRODUCT n
addmsg /kinetics/NMDAR /kinetics/transloc_2 SUBSTRATE n
addmsg /kinetics/CaMKII-PSD /kinetics/back_1 SUBSTRATE n
addmsg /kinetics/CaMKII/CaMKII /kinetics/back_1 PRODUCT n
addmsg /kinetics/NMDAR /kinetics/back_1 PRODUCT n
addmsg /kinetics/CaMKII-thr305-PSD /kinetics/back_2 SUBSTRATE n
addmsg /kinetics/CaMKII/CaMK-thr305 /kinetics/back_2 PRODUCT n
addmsg /kinetics/NMDAR /kinetics/back_2 PRODUCT n
addmsg /kinetics/CaMKII-thr286-PSD /kinetics/CaMKII-thr286-bind-CaM-PSD SUBSTRATE n
addmsg /kinetics/CaMKII-thr286-CaM-PSD /kinetics/CaMKII-thr286-bind-CaM-PSD PRODUCT n
addmsg /kinetics/CaM-Ca4-PSD /kinetics/CaMKII-thr286-bind-CaM-PSD SUBSTRATE n
addmsg /kinetics/CaM/CaM-TR2-bind-Ca-PSD /kinetics/CaM-TR2-Ca2-PSD REAC B A
addmsg /kinetics/CaM/CaM-TR2-Ca2-bind-Ca-PSD /kinetics/CaM-TR2-Ca2-PSD REAC A B
addmsg /kinetics/CaM/CaM-TR2-Ca2-bind-Ca-PSD /kinetics/CaM-Ca3-PSD REAC B A
addmsg /kinetics/CaM/CaM-Ca3-bind-Ca-PSD /kinetics/CaM-Ca3-PSD REAC A B
addmsg /kinetics/CaM/CaM-Ca3-bind-Ca-PSD /kinetics/CaM-Ca4-PSD REAC B A
addmsg /kinetics/CaMKII-thr286-bind-CaM-PSD /kinetics/CaM-Ca4-PSD REAC A B
addmsg /kinetics/CaMKII-bind-CaM-PSD /kinetics/CaM-Ca4-PSD REAC A B
addmsg /kinetics/equilib /kinetics/CaM-Ca4-PSD REAC A B
addmsg /kinetics/CaMKII-diss-CaM /kinetics/CaM-Ca4-PSD REAC B A
addmsg /kinetics/CaM/CaM-TR2-bind-Ca-PSD /kinetics/Ca-PSD REAC A B
addmsg /kinetics/CaM/CaM-TR2-bind-Ca-PSD /kinetics/Ca-PSD REAC A B
addmsg /kinetics/CaM/CaM-TR2-Ca2-bind-Ca-PSD /kinetics/Ca-PSD REAC A B
addmsg /kinetics/CaM/CaM-Ca3-bind-Ca-PSD /kinetics/Ca-PSD REAC A B
addmsg /kinetics/Ca_stoch_PSD /kinetics/Ca-PSD REAC B A
addmsg /kinetics/CaMKII-thr286-CaM-PSD /kinetics/286P-PSD SUMTOTAL n nInit
addmsg /kinetics/CaMKII-thr286-PSD /kinetics/286P-PSD SUMTOTAL n nInit
addmsg /kinetics/CaMKII-thr286-CaM-PSD /kinetics/actCaMKII-PSD SUMTOTAL n nInit
addmsg /kinetics/CaMKII-CaM-PSD /kinetics/actCaMKII-PSD SUMTOTAL n nInit
addmsg /kinetics/tot-auto-PSD /kinetics/actCaMKII-PSD SUMTOTAL n nInit
addmsg /kinetics/actCaMKII-PSD /kinetics/tot_CaMKII_PSD SUMTOTAL n nInit
addmsg /kinetics/CaMKII-PSD /kinetics/tot_CaMKII_PSD SUMTOTAL n nInit
addmsg /kinetics/CaMKII-thr305-PSD /kinetics/tot_CaMKII_PSD SUMTOTAL n nInit
addmsg /kinetics/CaMKII/CaMKII-CaM /kinetics/tot_CaMKII_cyt SUMTOTAL n nInit
addmsg /kinetics/CaMKII/CaMKII-thr286*-CaM /kinetics/tot_CaMKII_cyt SUMTOTAL n nInit
addmsg /kinetics/CaMKII/CaMKII-thr286 /kinetics/tot_CaMKII_cyt SUMTOTAL n nInit
addmsg /kinetics/CaMKII/CaMKII*** /kinetics/tot_CaMKII_cyt SUMTOTAL n nInit
addmsg /kinetics/CaMKII/CaMK-thr305 /kinetics/tot_CaMKII_cyt SUMTOTAL n nInit
addmsg /kinetics/CaMKII/CaMKII /kinetics/tot_CaMKII_cyt SUMTOTAL n nInit
addmsg /kinetics/basal_CaMKII_cyt /kinetics/tot_CaMKII_cyt SUMTOTAL n nInit
addmsg /kinetics/CaM-Ca4-PSD /kinetics/equilib SUBSTRATE n
addmsg /kinetics/CaM-Ca4 /kinetics/equilib PRODUCT n
addmsg /kinetics/PP1_PSD/dissoc-PP1-I1 /kinetics/PP1_PSD/I1 REAC B A
addmsg /kinetics/PKA-active/PKA-phosph-I1_PSD /kinetics/PP1_PSD/I1 REAC sA B
addmsg /kinetics/CaM_Ca_n-CaNAB/dephosph_inhib1_PSD /kinetics/PP1_PSD/I1 MM_PRD pA
addmsg /kinetics/PP2A/PP2A-dephosph-I1_PSD /kinetics/PP1_PSD/I1 MM_PRD pA
addmsg /kinetics/CaNAB-Ca4/dephosph_inhib1_noCaM_PSD /kinetics/PP1_PSD/I1 MM_PRD pA
addmsg /kinetics/Inact-PP1 /kinetics/PP1_PSD/I1* REAC A B
addmsg /kinetics/PKA-active/PKA-phosph-I1_PSD /kinetics/PP1_PSD/I1* MM_PRD pA
addmsg /kinetics/CaM_Ca_n-CaNAB/dephosph_inhib1_PSD /kinetics/PP1_PSD/I1* REAC sA B
addmsg /kinetics/PP2A/PP2A-dephosph-I1_PSD /kinetics/PP1_PSD/I1* REAC sA B
addmsg /kinetics/CaNAB-Ca4/dephosph_inhib1_noCaM_PSD /kinetics/PP1_PSD/I1* REAC sA B
addmsg /kinetics/Inact-PP1 /kinetics/PP1_PSD/PP1-I1* REAC B A
addmsg /kinetics/CaM_Ca_n-CaNAB/dephosph-PP1-I*_PSD /kinetics/PP1_PSD/PP1-I1* REAC sA B
addmsg /kinetics/PP2A/PP2A-dephosph-PP1-I*_PSD /kinetics/PP1_PSD/PP1-I1* REAC sA B
addmsg /kinetics/CaM_Ca_n-CaNAB/dephosph-PP1-I*_PSD /kinetics/PP1_PSD/PP1-I1 MM_PRD pA
addmsg /kinetics/PP2A/PP2A-dephosph-PP1-I*_PSD /kinetics/PP1_PSD/PP1-I1 MM_PRD pA
addmsg /kinetics/PP1_PSD/dissoc-PP1-I1 /kinetics/PP1_PSD/PP1-I1 REAC A B
addmsg /kinetics/PP1_PSD/I1 /kinetics/PP1_PSD/dissoc-PP1-I1 PRODUCT n
addmsg /kinetics/PP1-active_PSD /kinetics/PP1_PSD/dissoc-PP1-I1 PRODUCT n
addmsg /kinetics/PP1_PSD/PP1-I1 /kinetics/PP1_PSD/dissoc-PP1-I1 SUBSTRATE n
addmsg /kinetics/PP1_PSD/I1* /kinetics/Inact-PP1 SUBSTRATE n
addmsg /kinetics/PP1_PSD/PP1-I1* /kinetics/Inact-PP1 PRODUCT n
addmsg /kinetics/PP1-active_PSD /kinetics/Inact-PP1 SUBSTRATE n
addmsg /kinetics/PP1-active_PSD/Deph-thr286 /kinetics/PP1-active_PSD REAC eA B
addmsg /kinetics/PP1-active_PSD/Deph-thr286b /kinetics/PP1-active_PSD REAC eA B
addmsg /kinetics/PP1-active_PSD/Deph-thr305 /kinetics/PP1-active_PSD REAC eA B
addmsg /kinetics/PP1-active_PSD/Deph-thr305a /kinetics/PP1-active_PSD REAC eA B
addmsg /kinetics/PP1-active_PSD/Deph-thr286c /kinetics/PP1-active_PSD REAC eA B
addmsg /kinetics/PP1_PSD/dissoc-PP1-I1 /kinetics/PP1-active_PSD REAC B A
addmsg /kinetics/Inact-PP1 /kinetics/PP1-active_PSD REAC A B
addmsg /kinetics/PP1-active_PSD /kinetics/PP1-active_PSD/Deph-thr286 ENZYME n
addmsg /kinetics/CaMKII-thr286-CaM-PSD /kinetics/PP1-active_PSD/Deph-thr286 SUBSTRATE n
addmsg /kinetics/PP1-active_PSD /kinetics/PP1-active_PSD/Deph-thr286b ENZYME n
addmsg /kinetics/CaMKII-thr286-PSD /kinetics/PP1-active_PSD/Deph-thr286b SUBSTRATE n
addmsg /kinetics/PP1-active_PSD /kinetics/PP1-active_PSD/Deph-thr286c ENZYME n
addmsg /kinetics/CaMKII***-PSD /kinetics/PP1-active_PSD/Deph-thr286c SUBSTRATE n
addmsg /kinetics/PP1-active_PSD /kinetics/PP1-active_PSD/Deph-thr305a ENZYME n
addmsg /kinetics/CaMKII-thr305-PSD /kinetics/PP1-active_PSD/Deph-thr305a SUBSTRATE n
addmsg /kinetics/PP1-active_PSD /kinetics/PP1-active_PSD/Deph-thr305 ENZYME n
addmsg /kinetics/CaMKII***-PSD /kinetics/PP1-active_PSD/Deph-thr305 SUBSTRATE n
addmsg /kinetics/CaM-Ca3 /kinetics/CaM-Ca3-bind-Ca SUBSTRATE n
addmsg /kinetics/Ca /kinetics/CaM-Ca3-bind-Ca SUBSTRATE n
addmsg /kinetics/CaM-Ca4 /kinetics/CaM-Ca3-bind-Ca PRODUCT n
addmsg /kinetics/CaMKII/tot_CaM_CaMKII /kinetics/act_CaMKII_cyt SUMTOTAL n nInit
addmsg /kinetics/CaMKII/tot_autonomous_CaMKII /kinetics/act_CaMKII_cyt SUMTOTAL n nInit
addmsg /kinetics/transloc_2 /kinetics/NMDAR REAC A B
addmsg /kinetics/transloc_1 /kinetics/NMDAR REAC A B
addmsg /kinetics/back_1 /kinetics/NMDAR REAC B A
addmsg /kinetics/back_2 /kinetics/NMDAR REAC B A
addmsg /kinetics/CaMKII-CaM-PSD /kinetics/CaMKII-diss-CaM SUBSTRATE n
addmsg /kinetics/CaM-Ca4-PSD /kinetics/CaMKII-diss-CaM PRODUCT n
addmsg /kinetics/CaMKII-PSD /kinetics/CaMKII-diss-CaM PRODUCT n
addmsg /kinetics/CaM_Ca_n-CaNAB/dephosph_inhib1 /kinetics/CaM_Ca_n-CaNAB REAC eA B
addmsg /kinetics/CaM_Ca_n-CaNAB/dephosph-PP1-I* /kinetics/CaM_Ca_n-CaNAB REAC eA B
addmsg /kinetics/CaM_Ca_n-CaNAB/dephosph_inhib1_PSD /kinetics/CaM_Ca_n-CaNAB REAC eA B
addmsg /kinetics/CaM_Ca_n-CaNAB/dephosph-PP1-I*_PSD /kinetics/CaM_Ca_n-CaNAB REAC eA B
addmsg /kinetics/PP2B/CaMCa4-bind-CaNAB /kinetics/CaM_Ca_n-CaNAB REAC B A
addmsg /kinetics/CaM_Ca_n-CaNAB /kinetics/CaM_Ca_n-CaNAB/dephosph_inhib1 ENZYME n
addmsg /kinetics/PP1/I1* /kinetics/CaM_Ca_n-CaNAB/dephosph_inhib1 SUBSTRATE n
addmsg /kinetics/CaM_Ca_n-CaNAB /kinetics/CaM_Ca_n-CaNAB/dephosph-PP1-I* ENZYME n
addmsg /kinetics/PP1/PP1-I1* /kinetics/CaM_Ca_n-CaNAB/dephosph-PP1-I* SUBSTRATE n
addmsg /kinetics/CaM_Ca_n-CaNAB /kinetics/CaM_Ca_n-CaNAB/dephosph_inhib1_PSD ENZYME n
addmsg /kinetics/PP1_PSD/I1* /kinetics/CaM_Ca_n-CaNAB/dephosph_inhib1_PSD SUBSTRATE n
addmsg /kinetics/CaM_Ca_n-CaNAB /kinetics/CaM_Ca_n-CaNAB/dephosph-PP1-I*_PSD ENZYME n
addmsg /kinetics/PP1_PSD/PP1-I1* /kinetics/CaM_Ca_n-CaNAB/dephosph-PP1-I*_PSD SUBSTRATE n
addmsg /kinetics/Stoch_Basal_CaMKII_PSD /kinetics/basal_CaMKII_PSD REAC B A
addmsg /kinetics/Ca_stoch_cyt /kinetics/Ca_control_cyt REAC A B
addmsg /kinetics/Ca_control_cyt /kinetics/Ca_stoch_cyt SUBSTRATE n
addmsg /kinetics/Ca /kinetics/Ca_stoch_cyt PRODUCT n
addmsg /kinetics/Ca_stoch_PSD /kinetics/Ca_control_PSD REAC A B
addmsg /kinetics/Ca_control_PSD /kinetics/Ca_stoch_PSD SUBSTRATE n
addmsg /kinetics/Ca-PSD /kinetics/Ca_stoch_PSD PRODUCT n
addmsg /kinetics/Stoch_Basal_CaMKII_PSD /kinetics/basal_CaMKII_PSD_control REAC A B
addmsg /kinetics/basal_CaMKII_PSD_control /kinetics/Stoch_Basal_CaMKII_PSD SUBSTRATE n
addmsg /kinetics/basal_CaMKII_PSD /kinetics/Stoch_Basal_CaMKII_PSD PRODUCT n
addmsg /kinetics/CaMKII-thr286-CaM-PSD /kinetics/tot-CaM-CaMKII-PSD SUMTOTAL n nInit
addmsg /kinetics/CaMKII-CaM-PSD /kinetics/tot-CaM-CaMKII-PSD SUMTOTAL n nInit
addmsg /kinetics/tot-CaM-CaMKII-PSD/CaM-act-305-PSD /kinetics/tot-CaM-CaMKII-PSD REAC eA B
addmsg /kinetics/tot-CaM-CaMKII-PSD/CaM-act-286-PSD /kinetics/tot-CaM-CaMKII-PSD REAC eA B
addmsg /kinetics/tot-CaM-CaMKII-PSD/CaM_act_autoph /kinetics/tot-CaM-CaMKII-PSD REAC eA B
addmsg /kinetics/tot-CaM-CaMKII-PSD /kinetics/tot-CaM-CaMKII-PSD/CaM-act-305-PSD ENZYME n
addmsg /kinetics/CaMKII-thr286-PSD /kinetics/tot-CaM-CaMKII-PSD/CaM-act-305-PSD SUBSTRATE n
addmsg /kinetics/tot-CaM-CaMKII-PSD /kinetics/tot-CaM-CaMKII-PSD/CaM-act-286-PSD ENZYME n
addmsg /kinetics/CaMKII-CaM-PSD /kinetics/tot-CaM-CaMKII-PSD/CaM-act-286-PSD SUBSTRATE n
addmsg /kinetics/tot-CaM-CaMKII-PSD /kinetics/tot-CaM-CaMKII-PSD/CaM_act_autoph ENZYME n
addmsg /kinetics/CaMKII-PSD /kinetics/tot-CaM-CaMKII-PSD/CaM_act_autoph SUBSTRATE n
addmsg /kinetics/back_2 /kinetics/CaMKII-thr305-PSD REAC A B
addmsg /kinetics/PP1-active_PSD/Deph-thr305a /kinetics/CaMKII-thr305-PSD REAC sA B
addmsg /kinetics/PP1-active_PSD/Deph-thr286c /kinetics/CaMKII-thr305-PSD MM_PRD pA
addmsg /kinetics/actCaMKII-PSD /graphs/conc1/actCaMKII-PSD.Co PLOT Co *actCaMKII-PSD.Co *12
addmsg /kinetics/tot_CaMKII_PSD /graphs/conc1/tot_CaMKII_PSD.Co PLOT Co *tot_CaMKII_PSD.Co *23
addmsg /kinetics/act_CaMKII_cyt /graphs/conc1/act_CaMKII_cyt.Co PLOT Co *act_CaMKII_cyt.Co *14
addmsg /kinetics/tot_CaMKII_cyt /graphs/conc1/tot_CaMKII_cyt.Co PLOT Co *tot_CaMKII_cyt.Co *24
addmsg /kinetics/CaM_Ca_n-CaNAB /graphs/conc1/CaM_Ca_n-CaNAB.Co PLOT Co *CaM_Ca_n-CaNAB.Co *1
addmsg /kinetics/CaM-Ca4-PSD /graphs/conc2/CaM-Ca4-PSD.Co PLOT Co *CaM-Ca4-PSD.Co *blue
addmsg /kinetics/PP1-active_PSD /moregraphs/conc3/PP1-active_PSD.Co PLOT Co *PP1-active_PSD.Co *cyan
addmsg /kinetics/PKA-active /moregraphs/conc3/PKA-active.Co PLOT Co *PKA-active.Co *yellow
addmsg /kinetics/Ca /moregraphs/conc3/Ca.Co PLOT Co *Ca.Co *red
addmsg /kinetics/PP1-active /moregraphs/conc4/PP1-active.Co PLOT Co *PP1-active.Co *cyan
addmsg /kinetics/CaM-Ca4 /moregraphs/conc4/CaM-Ca4.Co PLOT Co *CaM-Ca4.Co *blue
enddump
// End of dump
call /kinetics/geometry/notes LOAD \
"Bulk spine volume here." \
""
call /kinetics/geometry[1]/notes LOAD \
"PSD geometry here."
call /kinetics/PP1-active/notes LOAD \
"Cohen et al Meth Enz 159 390-408 is main source of info" \
"conc = 1.8 uM"
call /kinetics/PKA-active/PKA-phosph-I1/notes LOAD \
"#s from Bramson et al CRC crit rev Biochem" \
"15:2 93-124. They have a huge list of peptide substrates" \
"and I have chosen high-ish rates." \
"These consts give too much PKA activity, so lower Vmax 1/3." \
"Now, k1 = 3e-5, k2 = 36, k3 = 9 (still pretty fast)." \
"Also lower Km 1/3 so k1 = 1e-5" \
"Cohen et al FEBS Lett 76:182-86 1977 say rate =30% PKA act on " \
"phosphokinase beta." \
""
call /kinetics/CaMKII/notes LOAD \
"Main reference here is the review by Hanson and Schulman, Ann Rev Biochem" \
"1992 vol 61 pp 559-601. Most of the mechanistic details and a few constants" \
"are derived from there. Many kinetics are from Hanson and Schulman JBC" \
"267:24 17216-17224 1992." \
"The enzs look a terrible mess. Actually it is just 3 reactions for diff sites," \
"by 4 states of CaMKII, defined by the phosph state."
call /kinetics/CaMKII/CaMKII/notes LOAD \
"Huge conc of CaMKII. In PSD it is 20-40% of protein, so we assume it is around" \
"2.5% of protein in spine as a whole. This level is so high it is unlikely to matter" \
"much if we are off a bit."
call /kinetics/CaMKII/CaMKII-thr286*-CaM/notes LOAD \
"From Hanson and Schulman, the thr286 is responsible for autonomous activation" \
"of CaMKII."
call /kinetics/CaMKII/CaMKII***/notes LOAD \
"From Hanson and Schulman, the CaMKII does a lot of autophosphorylation" \
"just after the CaM is released. This prevents further CaM binding and renders" \
"the enzyme quite independent of Ca."
call /kinetics/CaMKII/CaMKII-bind-CaM/notes LOAD \
"This is tricky. There is some cooperativity here arising from interactions" \
"between the subunits of the CAMKII holoenzyme. However, the" \
"stoichiometry is 1. " \
"Kb/Kf = 6e4 #/cell. Rate is fast (see Hanson et al Neuron 12 943-956 1994)" \
"so lets say kb = 10. This gives kf = 1.6667e-4" \
"H&S AnnRev Biochem 92 give tau for dissoc as 0.2 sec at low Ca, 0.4 at high." \
"Low Ca = 100 nM = physiol."
call /kinetics/CaMKII/CaMK-thr286-bind-CaM/notes LOAD \
"Affinity is up 1000X. Time to release is about 20 sec, so the kb is OK at 0.1" \
"This makes Kf around 1.6666e-3" \
""
call /kinetics/CaMKII/CaMKII-thr286/notes LOAD \
"I am not sure if we need to endow this one with a lot of enzs. It is likely" \
"to be a short-lived intermediate, since it will be phosphorylated further" \
"as soon as the CAM falls off."
call /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_305/notes LOAD \
"Rates from autocamtide phosphorylation, from " \
"Hanson and Schulman JBC 267:24 17216-17224 1992." \
"Jan 1 1998: Speed up 12x to match fig 5."
call /kinetics/CaMKII/tot_autonomous_CaMKII/auton_305/notes LOAD \
"See Hanson and Schulman again, for afterburst rates of" \
"phosph."
call /kinetics/CaMKII/CaMK-thr305/notes LOAD \
"This forms due to basal autophosphorylation, but I think it has to be" \
"considered as a pathway even if some CaM is floating around. In either" \
"case it will tend to block further binding of CaM, and will not display any" \
"enzyme activity. See Hanson and Schulman JBC 267:24 pp17216-17224 1992"
call /kinetics/CaM/CaM/notes LOAD \
"There is a LOT of this in the cell: upto 1% of total protein mass. (Alberts et al)" \
"Say 25 uM. Meyer et al Science 256 1199-1202 1992 refer to studies saying" \
"it is comparable to CaMK levels. " \
""
call /kinetics/CaM/CaM-TR2-bind-Ca/notes LOAD \
"Lets use the fast rate consts here. Since the rates are so different, I am not" \
"sure whether the order is relevant. These correspond to the TR2C fragment." \
"We use the Martin et al rates here, plus the Drabicowski binding consts." \
"All are scaled by 3X to cell temp." \
"kf = 2e-10 kb = 72" \
"Stemmer & Klee: K1=.9, K2=1.1. Assume 1.0uM for both. kb/kf=3.6e11." \
"If kb=72, kf = 2e-10 (Exactly the same !)...."
call /kinetics/CaM/CaM-TR2-Ca2-bind-Ca/notes LOAD \
"K3 = 21.5, K4 = 2.8. Assuming that the K4 step happens first, we get" \
"kb/kf = 2.8 uM = 1.68e6 so kf =6e-6 assuming kb = 10" \
""
call /kinetics/CaM/CaM-PSD/notes LOAD \
"There is a LOT of this in the cell: upto 1% of total protein mass. (Alberts et al)" \
"Say 25 uM. Meyer et al Science 256 1199-1202 1992 refer to studies saying" \
"it is comparable to CaMK levels. " \
""
call /kinetics/CaM/CaM-TR2-bind-Ca-PSD/notes LOAD \
"Lets use the fast rate consts here. Since the rates are so different, I am not" \
"sure whether the order is relevant. These correspond to the TR2C fragment." \
"We use the Martin et al rates here, plus the Drabicowski binding consts." \
"All are scaled by 3X to cell temp." \
"kf = 2e-10 kb = 72" \
"Stemmer & Klee: K1=.9, K2=1.1. Assume 1.0uM for both. kb/kf=3.6e11." \
"If kb=72, kf = 2e-10 (Exactly the same !)...."
call /kinetics/CaM/CaM-TR2-Ca2-bind-Ca-PSD/notes LOAD \
"K3 = 21.5, K4 = 2.8. Assuming that the K4 step happens first, we get" \
"kb/kf = 2.8 uM = 1.68e6 so kf =6e-6 assuming kb = 10" \
""
call /kinetics/CaM/CaM-Ca3-bind-Ca-PSD/notes LOAD \
"Use K3 = 21.5 uM here from Stemmer and Klee table 3." \
"kb/kf =21.5 * 6e5 so kf = 7.75e-7, kb = 10"
call /kinetics/CaM-TR2-Ca2/notes LOAD \
"This is the intermediate where the TR2 end (the high-affinity end) has" \
"bound the Ca but the TR1 end has not."
call /kinetics/PP1/I1/notes LOAD \
"I1 is a 'mixed' inhibitor, but at high enz concs it looks like a non-compet" \
"inhibitor (Foulkes et al Eur J Biochem 132 309-313 9183)." \
"We treat it as non-compet, so it just turns the enz off" \
"without interacting with the binding site." \
"Cohen et al ann rev bioch refer to results where conc is " \
"1.5 to 1.8 uM. In order to get complete inhib of PP1, which is at 1.8 uM," \
"we need >= 1.8 uM." \
"" \
""
call /kinetics/PP1/I1*/notes LOAD \
"Dephosph is mainly by PP2B"
call /kinetics/PP1/Inact-PP1/notes LOAD \
"K inhib = 1nM from Cohen Ann Rev Bioch 1989, " \
"4 nM from Foukes et al " \
"Assume 2 nM. kf /kb = 8.333e-4"
call /kinetics/PP1/dissoc-PP1-I1/notes LOAD \
"Let us assume that the equil in this case is very far over to the" \
"right. This is probably safe." \
""
call /kinetics/PP2A/PP2A-dephosph-I1/notes LOAD \
"PP2A does most of the dephosph of I1 at basal Ca levels. See" \
"the review by Cohen in Ann Rev Biochem 1989." \
"For now, lets halve Km. k1 was 3.3e-6, now 6.6e-6" \
""
call /kinetics/PP2A/PP2A-dephosph-PP1-I*/notes LOAD \
"k1 changed from 3.3e-6 to 6.6e-6" \
""
call /kinetics/PP2A/PP2A-dephosph-I1_PSD/notes LOAD \
"PP2A does most of the dephosph of I1 at basal Ca levels. See" \
"the review by Cohen in Ann Rev Biochem 1989." \
"For now, lets halve Km. k1 was 3.3e-6, now 6.6e-6" \
""
call /kinetics/PP2A/PP2A-dephosph-PP1-I*_PSD/notes LOAD \
"k1 changed from 3.3e-6 to 6.6e-6" \
""
call /kinetics/CaNAB-Ca4/dephosph_inhib1_noCaM/notes LOAD \
"The rates here are so slow I do not know if we should even bother" \
"with this enz reacn. These numbers are from Liu and Storm." \
"Other refs suggest that the Km stays the same" \
"but the Vmax goes to 10% of the CaM stim levels. " \
"Prev: k1=2.2e-9, k2 = 0.0052, k3 = 0.0013" \
"New : k1=5.7e-8, k2=.136, k3=.034"
call /kinetics/CaNAB-Ca4/dephosph_inhib1_noCaM_PSD/notes LOAD \
"The rates here are so slow I do not know if we should even bother" \
"with this enz reacn. These numbers are from Liu and Storm." \
"Other refs suggest that the Km stays the same" \
"but the Vmax goes to 10% of the CaM stim levels. " \
"Prev: k1=2.2e-9, k2 = 0.0052, k3 = 0.0013" \
"New : k1=5.7e-8, k2=.136, k3=.034"
call /kinetics/PP2B/notes LOAD \
"Also called Calcineurin." \
"Major sources of info:" \
"Cohen, P Ann Rev Biochem 1989 58:453-508" \
"Mumby and Walker Physiol Rev 73:4 673-699" \
"Stemmer and Klee Biochem 33 1994 6859-6866" \
"Liu and Storm JBC 264:22 1989 12800-12804" \
"This model is unusual: There is actually more expt info than I want to" \
"put in the model at this time." \
"Phosph: Hashimoto and Soderling JBC 1989 264:28 16624-16629 (Not used)"
call /kinetics/PP2B/CaNAB/notes LOAD \
"We assume that the A and B subunits of PP2B are always bound under" \
"physiol conditions." \
"Up to 1% of brain protein = 25 uM. I need to work out how it is distributed" \
"between cytosolic and particulate fractions." \
"Tallant and Cheung '83 Biochem 22 3630-3635 have conc in many " \
"species, average for mammalian brain is around 1 uM."
call /kinetics/PP2B/Ca-bind-CaNAB-Ca2/notes LOAD \
"This process is probably much more complicated and involves CaM." \
"However, as I can't find detailed info I am bundling this into a" \
"single step." \
"Based on Steemer and Klee pg 6863, the Kact is 0.5 uM." \
"kf/kb = 1/(0.5 * 6e5)^2 = 1.11e-11"
call /kinetics/PP2B/Ca-bind-CaNAB/notes LOAD \
"going on the experience with CaM, we put the fast (high affinity)" \
"sites first. We only know (Stemmer and Klee) that the affinity is < 70 nM." \
"Assuming 10 nM at first, we get" \
"kf = 2.78e-8, kb = 1." \
"Try 20 nM." \
"kf = 7e-9, kb = 1"
call /kinetics/transloc_1/notes LOAD \
"Rates to match curve in fig2 from Shen and Meyer, " \
"Science 284:162-166(1999)," \
"calculated for 6:1 alpha:beta CaMKII heterodimers" \
""
call /kinetics/transloc_2/notes LOAD \
"Same as for transloc_1" \
"" \
"" \
""
call /kinetics/back_1/notes LOAD \
"Rates set by the translocation experiments of " \
"Shen and Meyer, Science 1999."
call /kinetics/back_2/notes LOAD \
"Same as for back_1" \
""
call /kinetics/CaMKII-thr286-bind-CaM-PSD/notes LOAD \
"Same values as for the main compartment" \
"Can the main compartment pool of Ca/CaM be used?"
call /kinetics/CaM-TR2-Ca2-PSD/notes LOAD \
"This is the intermediate where the TR2 end (the high-affinity end) has" \
"bound the Ca but the TR1 end has not."
call /kinetics/equilib/notes LOAD \
"Diffusional equilibrium between PSD- and cytosolic compartment." \
"According to D. Bary in Cell Movements 2nd ed 2001 D for proteins" \
"is 5e-7 cm^2/s giving 10 ms for a translocation of 1 um. "
call /kinetics/PP1_PSD/I1/notes LOAD \
"I1 is a 'mixed' inhibitor, but at high enz concs it looks like a non-compet" \
"inhibitor (Foulkes et al Eur J Biochem 132 309-313 9183)." \
"We treat it as non-compet, so it just turns the enz off" \
"without interacting with the binding site." \
"Cohen et al ann rev bioch refer to results where conc is " \
"1.5 to 1.8 uM. In order to get complete inhib of PP1, which is at 1.8 uM," \
"we need >= 1.8 uM." \
"" \
""
call /kinetics/PP1_PSD/I1*/notes LOAD \
"Dephosph is mainly by PP2B"
call /kinetics/PP1_PSD/dissoc-PP1-I1/notes LOAD \
"Let us assume that the equil in this case is very far over to the" \
"right. This is probably safe." \
""
call /kinetics/Inact-PP1/notes LOAD \
"K inhib = 1nM from Cohen Ann Rev Bioch 1989, " \
"4 nM from Foukes et al " \
"Assume 2 nM. kf /kb = 8.333e-4"
call /kinetics/PP1-active_PSD/notes LOAD \
"Cohen et al Meth Enz 159 390-408 is main source of info" \
"conc = 1.8 uM"
call /kinetics/CaM-Ca3-bind-Ca/notes LOAD \
"Use K3 = 21.5 uM here from Stemmer and Klee table 3." \
"kb/kf =21.5 * 6e5 so kf = 7.75e-7, kb = 10"
call /kinetics/NMDAR/notes LOAD \
"The stochiometry is a bit off here. Each NMDAR actually" \
"binds to a holoenzyme, about 12 CaMKII subunits. But" \
"our CaMKII calculations are in terms of individual" \
"subunits. So as a hack, we put in much more NMDAR than" \
"is actually there."
call /kinetics/doqcsinfo/notes LOAD \
"This is the model of CaMKII bistability, model 3. It exhibits" \
"bistability in CaMKII activation due to autophosphorylation at the" \
"PSD and local saturation of PP1. This version" \
"of model 3 does not include the full PKA regulatory pathway," \
"and instead has a predefined initial amount of active PKA. "
complete_loading