// DOQCS : http://doqcs.ncbs.res.in/
// Accession Name = PKC_2003
// Accession Number = 48
// Transcriber = Upinder S. Bhalla, NCBS
// Developer = Upinder S. Bhalla, NCBS
// Species = Generic mammalian
// Tissue = Generic
// Cell Compartment = Cytosol + Cell membrane
// Notes = This model consists of receptor-ligand interaction, G-protein activation, Adenylyl cyclase mediated formation of cAMP and activation of PKA in the neuron. Demonstration programs using this model described in Bhalla US. (2004) Biophys J. 87(2):733-44 to generate a dose-response curve using stochastic calculations are available here.
//genesis
// kkit Version 11 flat dumpfile
// Saved on Fri Dec 9 11:10:36 2005
include kkit {argv 1}
FASTDT = 0.005
SIMDT = 0.005
CONTROLDT = 1
PLOTDT = 1
MAXTIME = 2000
TRANSIENT_TIME = 2
VARIABLE_DT_FLAG = 0
DEFAULT_VOL = 1.6667e-21
VERSION = 11.0
setfield /file/modpath value /home2/bhalla/scripts/modules
kparms
//genesis
initdump -version 3 -ignoreorphans 1
simobjdump doqcsinfo filename accessname accesstype transcriber developer \
citation species tissue cellcompartment methodology sources \
model_implementation model_validation x y z
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 xtree_fg_req xtree_textfg_req x y \
z
simobjdump kpool DiffConst CoInit Co n nInit mwt nMin vol slave_enable \
geomname 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
simundump geometry /kinetics/geometry 0 1e-15 3 sphere "" white black 3 10 0
simundump group /kinetics/PKC 0 blue black x 0 0 "" defaultfile defaultfile.g \
0 0 0 -3.0493 8.2163 0
simundump kpool /kinetics/PKC/PKC-Ca 0 0 3.7208e-17 3.7208e-17 2.2325e-11 \
2.2325e-11 0 0 6e+05 0 /kinetics/geometry red black -4.0752 1.5108 0
simundump kreac /kinetics/PKC/PKC-act-by-Ca 0 1e-06 0.5 "" white blue -4.0752 \
-0.12295 0
simundump kreac /kinetics/PKC/PKC-act-by-DAG 0 1.3333e-08 8.6348 "" white \
blue -2.0612 0.69395 0
simundump kreac /kinetics/PKC/PKC-Ca-to-memb 0 1.2705 3.5026 "" white blue \
-3.7974 4.2533 0
simundump kreac /kinetics/PKC/PKC-DAG-to-memb 0 1 0.1 "" white blue -2.6168 \
2.7362 0
simundump kreac /kinetics/PKC/PKC-act-by-Ca-AA 0 2e-09 0.1 "" white blue \
-0.78797 3.8157 0
simundump kreac /kinetics/PKC/PKC-act-by-DAG-AA 0 2 0.2 "" white blue 1.2492 \
3.2322 0
simundump kpool /kinetics/PKC/PKC-DAG-AA* 0 0 4.9137e-18 4.9137e-18 \
2.9482e-12 2.9482e-12 0 0 6e+05 0 /kinetics/geometry cyan blue 0.60098 \
5.537 0
simundump kpool /kinetics/PKC/PKC-Ca-AA* 0 0 1.75e-16 1.75e-16 1.05e-10 \
1.05e-10 0 0 6e+05 0 /kinetics/geometry orange blue -0.60278 6.2956 0
simundump kpool /kinetics/PKC/PKC-Ca-memb* 0 0 1.3896e-17 1.3896e-17 \
8.3376e-12 8.3376e-12 0 0 6e+05 0 /kinetics/geometry pink blue -2.7788 \
6.529 0
simundump kpool /kinetics/PKC/PKC-DAG-memb* 0 0 9.4352e-21 9.4352e-21 \
5.6611e-15 5.6611e-15 0 0 6e+05 0 /kinetics/geometry yellow blue -1.8297 \
5.5078 0
simundump kpool /kinetics/PKC/PKC-basal* 0 0 0.02 0.02 12000 12000 0 0 6e+05 \
0 /kinetics/geometry pink blue -4.7465 5.5662 0
simundump kreac /kinetics/PKC/PKC-basal-act 0 1 50 "" white blue -4.978 \
3.0571 0
simundump kpool /kinetics/PKC/PKC-AA* 0 0 1.8133e-17 1.8133e-17 1.088e-11 \
1.088e-11 0 0 6e+05 0 /kinetics/geometry cyan blue 1.7816 6.8207 0
simundump kreac /kinetics/PKC/PKC-act-by-AA 0 2e-10 0.1 "" white blue -4.9925 \
-1.8654 0
simundump kpool /kinetics/PKC/PKC-Ca-DAG 0 0 8.4632e-23 8.4632e-23 5.0779e-17 \
5.0779e-17 0 0 6e+05 0 /kinetics/geometry white blue 0.2306 1.8026 0
simundump kreac /kinetics/PKC/PKC-n-DAG 0 1e-09 0.1 "" white blue -3.0103 \
-1.9902 0
simundump kpool /kinetics/PKC/PKC-DAG 0 0 1.161e-16 1.161e-16 6.9661e-11 \
6.9661e-11 0 0 6e+05 0 /kinetics/geometry white blue -0.99631 -1.0857 0
simundump kreac /kinetics/PKC/PKC-n-DAG-AA 0 3e-08 2 "" white blue -1.2278 \
-2.9529 0
simundump kpool /kinetics/PKC/PKC-DAG-AA 0 0 2.5188e-19 2.5188e-19 1.5113e-13 \
1.5113e-13 0 0 6e+05 0 /kinetics/geometry white blue 0.62413 0.22715 0
simundump kpool /kinetics/PKC/PKC-cytosolic 0 0 1 1 6e+05 6e+05 0 0 6e+05 0 \
/kinetics/geometry white blue -6.1315 0.59711 0
simundump kpool /kinetics/DAG 1 0 11 11 6.6e+06 6.6e+06 0 0 6e+05 4 \
/kinetics/geometry green black -3.2051 -4.7168 0
simundump kpool /kinetics/Ca 1 0 0.08 0.08 48000 48000 0 0 6e+05 4 \
/kinetics/geometry red black -8.3874 -2.7634 0
simundump kpool /kinetics/AA 0 0 5 5 3e+06 3e+06 0 0 6e+05 4 \
/kinetics/geometry darkgreen black -3.2898 -9.3376 0
simundump kpool /kinetics/PKC-active 0 0 2.1222e-16 0.02 12000 1.2733e-10 0 0 \
6e+05 2 /kinetics/geometry yellow black 2.1325 8.477 0
simundump doqcsinfo /kinetics/doqcsinfo 0 db48.g PKC_2003 pathway \
"Upinder S. Bhalla, NCBS" "Upinder S. Bhalla, NCBS" "citation here" \
"Generic Mammalian" Generic "Cytosol + Cell membrane" Qualitative \
"Bhalla US. (2004) Biophys J. 87(2):733-44 ( peer-reviewed publication )" \
"Exact GENESIS implementation" "Approximates original data " 3 11 0
simundump xgraph /graphs/conc1 0 0 500 0 1 0
simundump xgraph /graphs/conc2 0 0 500 0 50 0
simundump xplot /graphs/conc1/PKC-active.Co 3 524288 \
"delete_plot.w ; edit_plot.D " yellow 0 0 1
simundump xgraph /moregraphs/conc3 0 0 500 0 1 0
simundump xgraph /moregraphs/conc4 0 0 500 0 1 0
simundump xcoredraw /edit/draw 0 -10.387 6 -11.338 12
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 \
"Demo for figures. Set up some plots." \
"Same as pkc46.g, fixed up plots, changed basal levels of DAG and" \
"AA"
addmsg /kinetics/PKC/PKC-act-by-Ca /kinetics/PKC/PKC-Ca REAC B A
addmsg /kinetics/PKC/PKC-act-by-DAG /kinetics/PKC/PKC-Ca REAC A B
addmsg /kinetics/PKC/PKC-Ca-to-memb /kinetics/PKC/PKC-Ca REAC A B
addmsg /kinetics/PKC/PKC-act-by-Ca-AA /kinetics/PKC/PKC-Ca REAC A B
addmsg /kinetics/PKC/PKC-cytosolic /kinetics/PKC/PKC-act-by-Ca SUBSTRATE n
addmsg /kinetics/Ca /kinetics/PKC/PKC-act-by-Ca SUBSTRATE n
addmsg /kinetics/PKC/PKC-Ca /kinetics/PKC/PKC-act-by-Ca PRODUCT n
addmsg /kinetics/DAG /kinetics/PKC/PKC-act-by-DAG SUBSTRATE n
addmsg /kinetics/PKC/PKC-Ca /kinetics/PKC/PKC-act-by-DAG SUBSTRATE n
addmsg /kinetics/PKC/PKC-Ca-DAG /kinetics/PKC/PKC-act-by-DAG PRODUCT n
addmsg /kinetics/PKC/PKC-Ca /kinetics/PKC/PKC-Ca-to-memb SUBSTRATE n
addmsg /kinetics/PKC/PKC-Ca-memb* /kinetics/PKC/PKC-Ca-to-memb PRODUCT n
addmsg /kinetics/PKC/PKC-Ca-DAG /kinetics/PKC/PKC-DAG-to-memb SUBSTRATE n
addmsg /kinetics/PKC/PKC-DAG-memb* /kinetics/PKC/PKC-DAG-to-memb PRODUCT n
addmsg /kinetics/PKC/PKC-Ca /kinetics/PKC/PKC-act-by-Ca-AA SUBSTRATE n
addmsg /kinetics/AA /kinetics/PKC/PKC-act-by-Ca-AA SUBSTRATE n
addmsg /kinetics/PKC/PKC-Ca-AA* /kinetics/PKC/PKC-act-by-Ca-AA PRODUCT n
addmsg /kinetics/PKC/PKC-DAG-AA* /kinetics/PKC/PKC-act-by-DAG-AA PRODUCT n
addmsg /kinetics/PKC/PKC-DAG-AA /kinetics/PKC/PKC-act-by-DAG-AA SUBSTRATE n
addmsg /kinetics/PKC/PKC-act-by-DAG-AA /kinetics/PKC/PKC-DAG-AA* REAC B A
addmsg /kinetics/PKC/PKC-act-by-Ca-AA /kinetics/PKC/PKC-Ca-AA* REAC B A
addmsg /kinetics/PKC/PKC-Ca-to-memb /kinetics/PKC/PKC-Ca-memb* REAC B A
addmsg /kinetics/PKC/PKC-DAG-to-memb /kinetics/PKC/PKC-DAG-memb* REAC B A
addmsg /kinetics/PKC/PKC-basal-act /kinetics/PKC/PKC-basal* REAC B A
addmsg /kinetics/PKC/PKC-cytosolic /kinetics/PKC/PKC-basal-act SUBSTRATE n
addmsg /kinetics/PKC/PKC-basal* /kinetics/PKC/PKC-basal-act PRODUCT n
addmsg /kinetics/PKC/PKC-act-by-AA /kinetics/PKC/PKC-AA* REAC B A
addmsg /kinetics/AA /kinetics/PKC/PKC-act-by-AA SUBSTRATE n
addmsg /kinetics/PKC/PKC-AA* /kinetics/PKC/PKC-act-by-AA PRODUCT n
addmsg /kinetics/PKC/PKC-cytosolic /kinetics/PKC/PKC-act-by-AA SUBSTRATE n
addmsg /kinetics/PKC/PKC-act-by-DAG /kinetics/PKC/PKC-Ca-DAG REAC B A
addmsg /kinetics/PKC/PKC-DAG-to-memb /kinetics/PKC/PKC-Ca-DAG REAC A B
addmsg /kinetics/PKC/PKC-cytosolic /kinetics/PKC/PKC-n-DAG SUBSTRATE n
addmsg /kinetics/DAG /kinetics/PKC/PKC-n-DAG SUBSTRATE n
addmsg /kinetics/PKC/PKC-DAG /kinetics/PKC/PKC-n-DAG PRODUCT n
addmsg /kinetics/PKC/PKC-n-DAG /kinetics/PKC/PKC-DAG REAC B A
addmsg /kinetics/PKC/PKC-n-DAG-AA /kinetics/PKC/PKC-DAG REAC A B
addmsg /kinetics/PKC/PKC-DAG /kinetics/PKC/PKC-n-DAG-AA SUBSTRATE n
addmsg /kinetics/AA /kinetics/PKC/PKC-n-DAG-AA SUBSTRATE n
addmsg /kinetics/PKC/PKC-DAG-AA /kinetics/PKC/PKC-n-DAG-AA PRODUCT n
addmsg /kinetics/PKC/PKC-n-DAG-AA /kinetics/PKC/PKC-DAG-AA REAC B A
addmsg /kinetics/PKC/PKC-act-by-DAG-AA /kinetics/PKC/PKC-DAG-AA REAC A B
addmsg /kinetics/PKC/PKC-act-by-Ca /kinetics/PKC/PKC-cytosolic REAC A B
addmsg /kinetics/PKC/PKC-basal-act /kinetics/PKC/PKC-cytosolic REAC A B
addmsg /kinetics/PKC/PKC-act-by-AA /kinetics/PKC/PKC-cytosolic REAC A B
addmsg /kinetics/PKC/PKC-n-DAG /kinetics/PKC/PKC-cytosolic REAC A B
addmsg /kinetics/PKC/PKC-act-by-DAG /kinetics/DAG REAC A B
addmsg /kinetics/PKC/PKC-n-DAG /kinetics/DAG REAC A B
addmsg /kinetics/PKC/PKC-act-by-Ca /kinetics/Ca REAC A B
addmsg /kinetics/PKC/PKC-act-by-Ca-AA /kinetics/AA REAC A B
addmsg /kinetics/PKC/PKC-act-by-AA /kinetics/AA REAC A B
addmsg /kinetics/PKC/PKC-n-DAG-AA /kinetics/AA REAC A B
addmsg /kinetics/PKC/PKC-DAG-AA* /kinetics/PKC-active SUMTOTAL n nInit
addmsg /kinetics/PKC/PKC-Ca-memb* /kinetics/PKC-active SUMTOTAL n nInit
addmsg /kinetics/PKC/PKC-Ca-AA* /kinetics/PKC-active SUMTOTAL n nInit
addmsg /kinetics/PKC/PKC-DAG-memb* /kinetics/PKC-active SUMTOTAL n nInit
addmsg /kinetics/PKC/PKC-basal* /kinetics/PKC-active SUMTOTAL n nInit
addmsg /kinetics/PKC/PKC-AA* /kinetics/PKC-active SUMTOTAL n nInit
addmsg /kinetics/PKC-active /graphs/conc1/PKC-active.Co PLOT Co *PKC-active.Co *yellow
enddump
// End of dump
call /kinetics/PKC/PKC-act-by-Ca/notes LOAD \
"Need est of rate of assoc of Ca and PKC. Assume it is fast" \
"The original parameter-searched kf of 439.4 has been" \
"scaled by 1/6e8 to account for change of units to n. Kf now 8.16e-7, kb=.6085" \
"Raised kf to 1e-6 to match Ca curve, kb to .5" \
""
call /kinetics/PKC/PKC-act-by-DAG/notes LOAD \
"Need est of rate. Assume it is fast" \
"Obtained from param search" \
"kf raised 10 X : see Shinomura et al PNAS 88 5149-5153 1991." \
"kf changed from 3.865e-7 to 2.0e-7 in line with closer analysis of" \
"Shinomura data." \
"26 June 1996: Corrected DAG data: reduce kf 15x from " \
"2e-7 to 1.333e-8"
call /kinetics/PKC/PKC-DAG-to-memb/notes LOAD \
"Raise kb from .087 to 0.1 to match data from Shinomura et al." \
"Lower kf from 1.155 to 1.0 to match data from Shinomura et al."
call /kinetics/PKC/PKC-act-by-Ca-AA/notes LOAD \
"Schaechter and Benowitz We have to increase Kf for conc scaling" \
"Changed kf to 2e-9 on Sept 19, 94. This gives better match." \
""
call /kinetics/PKC/PKC-act-by-DAG-AA/notes LOAD \
"Assume slowish too. Schaechter and Benowitz"
call /kinetics/PKC/PKC-basal-act/notes LOAD \
"Initial basal levels were set by kf = 1, kb = 20. In model, though, the" \
"basal levels of PKC activity are higher."
call /kinetics/PKC/PKC-act-by-AA/notes LOAD \
"Raise kf from 1.667e-10 to 2e-10 to get better match to data."
call /kinetics/PKC/PKC-n-DAG/notes LOAD \
"kf raised 10 X based on Shinomura et al PNAS 88 5149-5153 1991" \
"closer analysis of Shinomura et al: kf now 1e-8 (was 1.66e-8)." \
"Further tweak. To get sufficient AA synergy, increase kf to 1.5e-8" \
"26 June 1996: Corrected DAG levels: reduce kf by 15x from" \
"1.5e-8 to 1e-9"
call /kinetics/PKC/PKC-DAG/notes LOAD \
"CoInit was .0624" \
""
call /kinetics/PKC/PKC-n-DAG-AA/notes LOAD \
"Reduced kf to 0.66X to match Shinomura et al data." \
"Initial: kf = 3.3333e-9" \
"New: 2e-9" \
"Newer: 2e-8" \
"kb was 0.2" \
"now 2."
call /kinetics/PKC/PKC-cytosolic/notes LOAD \
"Marquez et al J. Immun 149,2560(92) est 1e6/cell for chromaffin cells" \
"We will use 1 uM as our initial concen" \
""
call /kinetics/DAG/notes LOAD \
"The conc of this has been a problem. Schaecter and Benowitz use 50 uM," \
"but Shinomura et al have < 5. So I have altered the DAG-dependent " \
"rates in the PKC model to reflect this."
call /kinetics/PKC-active/notes LOAD \
"Conc of PKC in brain is about 1 uM (?)"
call /kinetics/doqcsinfo/notes LOAD \
" This model consists of receptor-ligand interaction, G-protein activation, Adenylyl cyclase mediated formation of cAMP and activation of PKA in the neuron. Demonstration programs using this model described in Bhalla US. (2004) Biophys J. 87(2):733-44 to generate a dose-response curve using stochastic calculations are available here."
complete_loading