//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