//genesis
// kkit Version 11 flat dumpfile
// Saved on Wed Jul 6 15:52:49 2005
include kkit {argv 1}
FASTDT = 0.0001
SIMDT = 0.01
CONTROLDT = 100
PLOTDT = 60
MAXTIME = 10000
TRANSIENT_TIME = 2
VARIABLE_DT_FLAG = 0
DEFAULT_VOL = 1e-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/dendrite_geometry 0 5e-18 3 cylinder "" -8 -6 0
simundump geometry /kinetics/spine_geometry 0 9e-20 3 sphere "" -8 -3 0
simundump geometry /kinetics/PSD_geometry 0 1e-20 3 sphere "" -8 3 0
simundump group /kinetics/Membrane 0 yellow black x 0 1 "" Membrane \
defaultfile.g 0 0 0 10 3 0
simundump kpool /kinetics/Membrane/PP1-active 0 0 0.33333 0.33333 2 2 0 0 6 0 \
/kinetics/PSD_geometry cyan yellow -2 1 0
simundump kenz /kinetics/Membrane/PP1-active/PP1 0 0 0 0 0 5.9999 0.29167 1.4 \
0.35 0 0 "" red cyan "" -2 2 0
simundump kenz /kinetics/Membrane/PP1-active/PP1[1] 0 0 0 0 0 5.9999 0.29167 \
1.4 0.35 0 0 "" red cyan "" 4 2 0
simundump kpool /kinetics/Membrane/MR* 0 0 0 0 0 0 0 0 6 0 \
/kinetics/PSD_geometry 9 yellow 1 3 0
simundump kpool /kinetics/Membrane/MR 0 0 0 0 0 0 0 0 6 0 \
/kinetics/PSD_geometry 1 yellow -5 3 0
simundump kpool /kinetics/Membrane/MR** 0 0 0 0 0 0 0 0 6 0 \
/kinetics/PSD_geometry blue yellow 7 3 0
simundump group /kinetics/Internal 0 15 black x 0 1 "" Internal defaultfile.g \
0 0 0 10 -3 0
simundump kpool /kinetics/Internal/IR** 0 0 0 0 0 0 0 0 54 0 \
/kinetics/spine_geometry 50 15 7 -3 0
simundump kpool /kinetics/Internal/IR 0 0 0 0 0 0 0 0 54 0 \
/kinetics/spine_geometry 30 15 -5 -3 0
simundump kpool /kinetics/Internal/IR* 0 0 0 0 0 0 0 0 54 0 \
/kinetics/spine_geometry 54 15 1 -3 0
simundump kpool /kinetics/PKA-active 0 0 0.018519 0.018519 1 1 0 0 54 4 \
/kinetics/spine_geometry 47 black -8 0 0
simundump kenz /kinetics/PKA-active/memb-PKA-act 0 0 0 0 0 5.9999 0.14815 24 \
6 0 0 "" red 47 "" -2 4 0
simundump kenz /kinetics/PKA-active/internal-PKA-act 0 0 0 0 0 5.9999 0.14815 \
24 6 0 0 "" red 47 "" -2 -2 0
simundump kenz /kinetics/PKA-active/memb-PKA-act[1] 0 0 0 0 0 5.9999 0.14815 \
24 6 0 0 "" red 47 "" 4 4 0
simundump kenz /kinetics/PKA-active/internal-PKA-act[1] 0 0 0 0 0 5.9999 \
0.14815 24 6 0 0 "" red 47 "" 4 -2 0
simundump kreac /kinetics/to_memb 0 0.0002 0.008 "" white black 7 0 0
simundump kreac /kinetics/from_memb 0 0.0008 0 "" white black -5 0 0
simundump kpool /kinetics/Anchor 0 0 27.333 27.333 164 164 0 0 6 0 \
/kinetics/PSD_geometry 60 black 1 -1 0
simundump kreac /kinetics/exchange 0 0.018 1 "" white black -7 -4 0
simundump kpool /kinetics/Bulk_AMPAR 0 0 0.003 0.003 9 9 0 0 3000 4 \
/kinetics/dendrite_geometry blue black -2 -6 0
simundump kreac /kinetics/degradation[1] 0 2e-05 0 "" white black 4 -4 0
simundump kreac /kinetics/degradation 0 2e-05 0 "" white black -2 -4 0
simundump doqcsinfo /kinetics/doqcsinfo 0 model2_db.g \
simple_AMPAR_traff_model2 network "Upinder S. Bhalla, NCBS" \
"Upinder S. Bhalla, NCBS" "Hayer and Bhalla, PLoS Comput. Biol. 2005" \
"General Mammalian" Neuronal "Postsynaptic Density, Synaptic Spine" \
Illustrative "Hayer A, Bhalla US PLoS Comput Biol. 2005 Jul;1(2):137-54. Epub 2005 Jul 29. ( Peer-reviewed publication )" "Exact GENESIS implementation" \
"Approximates original data " show_dumpdb
simundump xgraph /graphs/conc1 0 0 47000 0 30 0
simundump xgraph /graphs/conc2 0 0 47000 0 5 0
simundump xplot /graphs/conc1/MR.Co 3 524288 \
"delete_plot.w ; edit_plot.D " 1 0 0 1
simundump xplot /graphs/conc1/MR*.Co 3 524288 \
"delete_plot.w ; edit_plot.D " 9 0 0 1
simundump xplot /graphs/conc1/MR**.Co 3 524288 \
"delete_plot.w ; edit_plot.D " blue 0 0 1
simundump xplot /graphs/conc2/IR.Co 3 524288 \
"delete_plot.w ; edit_plot.D " 30 0 0 1
simundump xplot /graphs/conc2/IR*.Co 3 524288 \
"delete_plot.w ; edit_plot.D " 54 0 0 1
simundump xplot /graphs/conc2/IR**.Co 3 524288 \
"delete_plot.w ; edit_plot.D " 50 0 0 1
simundump xgraph /moregraphs/conc3 0 0 47000 0 1 0
simundump xgraph /moregraphs/conc4 0 0 47000 0 1 0
simundump xplot /moregraphs/conc3/PKA-active.Co 3 524288 \
"delete_plot.w ; edit_plot.D " 47 0 0 1
simundump xplot /moregraphs/conc3/Anchor.Co 3 524288 \
"delete_plot.w ; edit_plot.D " 60 0 0 1
simundump xplot /moregraphs/conc3/PP1-active.Co 3 524288 \
"delete_plot.w ; edit_plot.D " cyan 0 0 1
simundump xplot /moregraphs/conc3/PP1_1.CoComplex 3 524288 \
"delete_plot.w ; edit_plot.D " red 0 0 1
simundump xplot /moregraphs/conc3/PP1.CoComplex 3 524288 \
"delete_plot.w ; edit_plot.D " red 0 0 1
simundump xplot /moregraphs/conc4/Bulk_AMPAR.Co 3 524288 \
"delete_plot.w ; edit_plot.D " blue 0 0 1
simundump xcoredraw /edit/draw 0 -10 12 -8 6
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 \
"Aug 24 2004." \
"Slowly building up. Intermediate save with some more rates." \
"Volumes set up." \
"Saved as AMPA_traff2.g," \
"First test" \
"AMPA_traff3.g" \
"Next:" \
"AMPA_traff4.g" \
"The current version exhibits rather nice sharp thresholding" \
"around 0.15 uM PKA. If Anchor is buffered at 150 it has a" \
"zeroth order transition around 0.1 uM PKA. Saved as" \
"AMPA_traff6.g" \
"" \
"25 Aug 2004" \
"Tried second-order interaction between anchor and receptor." \
"Saved as AMPA_traff7.g" \
"" \
"Intermediate save: AMPA_traff8.g" \
"" \
"26 Aug 2004. " \
"A functioning bistable system." \
"AMPA_traff9.g" \
"" \
"27 Aug 2004" \
"AMPAR_traf11.g" \
"First pass at completely different version, with 2 phosph states" \
"and first-order trafficking, more like the original full-scale" \
"model. This version looks nearly bistable, but actually has a" \
"runaway buildup from resting levels if you leave it long enough." \
"" \
"AMPAR_traff12.g" \
"Simple addition of degradation steps. Now it is bona-fide" \
"bistable." \
"" \
"5 March 2005. Based on AMPAR_traff12.g, trying to plug in" \
"parameters from transloc_feb05k.g. Now it is no longer bistable." \
"Temporary save in AMPA_traff_mar_a.g" \
"" \
"13 March 2005. Based on AMPA_traff_mar_a.g. Lowered degradation" \
"rate from 3.6e-5 to 2e-5. Set Bulk_AMPAR to 0.8 from 0.5. " \
"Added some plots. Saved as" \
"AMPA_traff_13mar_2005.g" \
"" \
"2 June 2005. Halved enzyme Km for PKA and PP1. This is because" \
"each reaction actually represents the phosphorylation/" \
"dephosphorylation of two possible subunits rather than one." \
"this version is bistable, but the level of Bulk AMPAR has to" \
"be reduced. Here it is 0.2" \
"Saved as simple_AMPA_02jun05.g" \
"" \
"16 June 2005. Moved Bulk_AMPAR to dendrite compartment. Did" \
"appropriate scaling of volumes and exchange rates to keep" \
"model consistent with earlier version. Lowered the Bulk_AMPAR conc" \
"a little, to 9 molecules, to compensate for the changes in Km " \
"for PKA. Saved as simple_AMPAR_traff.g" \
"" \
"" \
""
addmsg /kinetics/Membrane/PP1-active/PP1 /kinetics/Membrane/PP1-active REAC eA B
addmsg /kinetics/Membrane/PP1-active/PP1[1] /kinetics/Membrane/PP1-active REAC eA B
addmsg /kinetics/Membrane/PP1-active /kinetics/Membrane/PP1-active/PP1 ENZYME n
addmsg /kinetics/Membrane/MR* /kinetics/Membrane/PP1-active/PP1 SUBSTRATE n
addmsg /kinetics/Membrane/PP1-active /kinetics/Membrane/PP1-active/PP1[1] ENZYME n
addmsg /kinetics/Membrane/MR** /kinetics/Membrane/PP1-active/PP1[1] SUBSTRATE n
addmsg /kinetics/PKA-active/memb-PKA-act /kinetics/Membrane/MR* MM_PRD pA
addmsg /kinetics/Membrane/PP1-active/PP1 /kinetics/Membrane/MR* REAC sA B
addmsg /kinetics/PKA-active/memb-PKA-act[1] /kinetics/Membrane/MR* REAC sA B
addmsg /kinetics/Membrane/PP1-active/PP1[1] /kinetics/Membrane/MR* MM_PRD pA
addmsg /kinetics/PKA-active/memb-PKA-act /kinetics/Membrane/MR REAC sA B
addmsg /kinetics/Membrane/PP1-active/PP1 /kinetics/Membrane/MR MM_PRD pA
addmsg /kinetics/from_memb /kinetics/Membrane/MR REAC A B
addmsg /kinetics/PKA-active/memb-PKA-act[1] /kinetics/Membrane/MR** MM_PRD pA
addmsg /kinetics/to_memb /kinetics/Membrane/MR** REAC B A
addmsg /kinetics/Membrane/PP1-active/PP1[1] /kinetics/Membrane/MR** REAC sA B
addmsg /kinetics/PKA-active/internal-PKA-act[1] /kinetics/Internal/IR** MM_PRD pA
addmsg /kinetics/to_memb /kinetics/Internal/IR** REAC A B
addmsg /kinetics/degradation[1] /kinetics/Internal/IR** REAC A B
addmsg /kinetics/PKA-active/internal-PKA-act /kinetics/Internal/IR REAC sA B
addmsg /kinetics/exchange /kinetics/Internal/IR REAC B A
addmsg /kinetics/from_memb /kinetics/Internal/IR REAC B A
addmsg /kinetics/PKA-active/internal-PKA-act /kinetics/Internal/IR* MM_PRD pA
addmsg /kinetics/PKA-active/internal-PKA-act[1] /kinetics/Internal/IR* REAC sA B
addmsg /kinetics/degradation /kinetics/Internal/IR* REAC A B
addmsg /kinetics/PKA-active/memb-PKA-act /kinetics/PKA-active REAC eA B
addmsg /kinetics/PKA-active/internal-PKA-act /kinetics/PKA-active REAC eA B
addmsg /kinetics/PKA-active/memb-PKA-act[1] /kinetics/PKA-active REAC eA B
addmsg /kinetics/PKA-active/internal-PKA-act[1] /kinetics/PKA-active REAC eA B
addmsg /kinetics/PKA-active /kinetics/PKA-active/memb-PKA-act ENZYME n
addmsg /kinetics/Membrane/MR /kinetics/PKA-active/memb-PKA-act SUBSTRATE n
addmsg /kinetics/PKA-active /kinetics/PKA-active/internal-PKA-act ENZYME n
addmsg /kinetics/Internal/IR /kinetics/PKA-active/internal-PKA-act SUBSTRATE n
addmsg /kinetics/PKA-active /kinetics/PKA-active/memb-PKA-act[1] ENZYME n
addmsg /kinetics/Membrane/MR* /kinetics/PKA-active/memb-PKA-act[1] SUBSTRATE n
addmsg /kinetics/PKA-active /kinetics/PKA-active/internal-PKA-act[1] ENZYME n
addmsg /kinetics/Internal/IR* /kinetics/PKA-active/internal-PKA-act[1] SUBSTRATE n
addmsg /kinetics/Anchor /kinetics/to_memb SUBSTRATE n
addmsg /kinetics/Membrane/MR** /kinetics/to_memb PRODUCT n
addmsg /kinetics/Internal/IR** /kinetics/to_memb SUBSTRATE n
addmsg /kinetics/Anchor /kinetics/from_memb PRODUCT n
addmsg /kinetics/Membrane/MR /kinetics/from_memb SUBSTRATE n
addmsg /kinetics/Internal/IR /kinetics/from_memb PRODUCT n
addmsg /kinetics/from_memb /kinetics/Anchor REAC B A
addmsg /kinetics/to_memb /kinetics/Anchor REAC A B
addmsg /kinetics/Bulk_AMPAR /kinetics/exchange SUBSTRATE n
addmsg /kinetics/Internal/IR /kinetics/exchange PRODUCT n
addmsg /kinetics/exchange /kinetics/Bulk_AMPAR REAC A B
addmsg /kinetics/degradation /kinetics/Bulk_AMPAR REAC B A
addmsg /kinetics/degradation[1] /kinetics/Bulk_AMPAR REAC B A
addmsg /kinetics/Internal/IR** /kinetics/degradation[1] SUBSTRATE n
addmsg /kinetics/Bulk_AMPAR /kinetics/degradation[1] PRODUCT n
addmsg /kinetics/Internal/IR* /kinetics/degradation SUBSTRATE n
addmsg /kinetics/Bulk_AMPAR /kinetics/degradation PRODUCT n
addmsg /kinetics/Membrane/MR /graphs/conc1/MR.Co PLOT Co *MR.Co *1
addmsg /kinetics/Membrane/MR* /graphs/conc1/MR*.Co PLOT Co *MR*.Co *9
addmsg /kinetics/Membrane/MR** /graphs/conc1/MR**.Co PLOT Co *MR**.Co *blue
addmsg /kinetics/Internal/IR /graphs/conc2/IR.Co PLOT Co *IR.Co *30
addmsg /kinetics/Internal/IR* /graphs/conc2/IR*.Co PLOT Co *IR*.Co *54
addmsg /kinetics/Internal/IR** /graphs/conc2/IR**.Co PLOT Co *IR**.Co *50
addmsg /kinetics/PKA-active /moregraphs/conc3/PKA-active.Co PLOT Co *PKA-active.Co *47
addmsg /kinetics/Anchor /moregraphs/conc3/Anchor.Co PLOT Co *Anchor.Co *60
addmsg /kinetics/Membrane/PP1-active /moregraphs/conc3/PP1-active.Co PLOT Co *PP1-active.Co *cyan
addmsg /kinetics/Membrane/PP1-active/PP1[1] /moregraphs/conc3/PP1_1.CoComplex PLOT CoComplex *PP1_1.CoComplex *red
addmsg /kinetics/Membrane/PP1-active/PP1 /moregraphs/conc3/PP1.CoComplex PLOT CoComplex *PP1.CoComplex *red
addmsg /kinetics/Bulk_AMPAR /moregraphs/conc4/Bulk_AMPAR.Co PLOT Co *Bulk_AMPAR.Co *blue
enddump
// End of dump
call /kinetics/Membrane/PP1-active/PP1/notes LOAD \
"Note that Km is halved from 2 to 1, as compared to " \
"original detailed model. This is because each substrate" \
"represents two subunits of the original detailed model." \
""
call /kinetics/Membrane/PP1-active/PP1[1]/notes LOAD \
"Note halving of Km from 2 to 1. See also" \
" notes for internal-PKA-act." \
"Basically, the enzyme must act on two substrate subunits" \
"which are lumped in the current simplification of the" \
"original detailed model. We thank an anonymous reviewer" \
"for pointing this out."
call /kinetics/PKA-active/memb-PKA-act/notes LOAD \
"Note halving of Km. See notes for internal-PKA-act enzymatic" \
"step."
call /kinetics/PKA-active/internal-PKA-act/notes LOAD \
"Note that Km is halved from the main model, from 7.5 to " \
"3.75. This is because here we lump two subunits into one," \
"thus double the effective substrate conc that the enzyme" \
"must deal with. We thank an anonymous reviewer for pointing" \
"this out."
call /kinetics/PKA-active/memb-PKA-act[1]/notes LOAD \
"Note halving of Km. See notes for internal-PKA-act enzyme" \
"step."
call /kinetics/PKA-active/internal-PKA-act[1]/notes LOAD \
"Note that Km is halved from the detailed model," \
" as the reaction represents enzyme" \
"activity on 2 subunits."
call /kinetics/doqcsinfo/notes LOAD \
"This is a highly simplified model of the AMPAR trafficking cycle" \
"that exhibits bistability. It is model 2 from Hayer and Bhalla," \
"PLoS 2005. Its main purpose it to illustrate how the bistability" \
"arises."
complete_loading