// DOQCS :http://doqcs.ncbs.res.in/
// Accession Name = cAMP_pathway
// Accession Number = 25
// Pathway Name = PKA
// Pathway Number = 135
// Transcriber = Upinder S. Bhalla, NCBS
// Developer = Upinder S. Bhalla, NCBS
// Species = Generic mammalian
// Tissue = Brain - Neuronal
// Cell Compartment = Cell membrane + Cytosol
// Notes = General ref: Taylor et al Ann Rev Biochem 1990 59:971-1005
//genesis
// kkit Version 11 flat dumpfile
// Saved on Wed Feb 22 16:19:56 2006
include kkit {argv 1}
FASTDT = 0.001
SIMDT = 0.001
CONTROLDT = 1
PLOTDT = 1
MAXTIME = 1000
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 -6 -6 0
simundump group /kinetics/PKA 0 blue blue x 0 0 "" defaultfile defaultfile.g \
0 0 0 -11.636 -12.25 0
simundump kpool /kinetics/PKA/R2C2 0 0 0.5 0.5 3e+05 3e+05 0 0 6e+05 0 \
/kinetics/geometry white blue -16.348 -19.323 0
simundump kreac /kinetics/PKA/cAMP-bind-site-B1 0 9e-05 33 "" white blue \
-13.972 -22.598 0
simundump kreac /kinetics/PKA/cAMP-bind-site-B2 1 9e-05 33 "" white blue \
-11.63 -21.35 0
simundump kreac /kinetics/PKA/cAMP-bind-site-A1 1 0.000125 110 "" white blue \
-8.9437 -22.535 0
simundump kreac /kinetics/PKA/cAMP-bind-site-A2 1 0.000125 32.5 "" white blue \
-5.6565 -21.104 0
simundump kreac /kinetics/PKA/Release-C1 1 60 3e-05 "" white blue -5.0539 \
-14.46 0
simundump kreac /kinetics/PKA/Release-C2 1 60 3e-05 "" white blue -9.9249 \
-15.738 0
simundump kpool /kinetics/PKA/PKA-inhibitor 1 0 0.25 0.25 1.5e+05 1.5e+05 0 0 \
6e+05 0 /kinetics/geometry cyan blue -14.407 -14.871 0
simundump kreac /kinetics/PKA/inhib-PKA 1 1e-04 1 "" white blue -11.613 \
-14.248 0
simundump kpool /kinetics/PKA/inhibited-PKA 1 0 0 0 0 0 0 0 6e+05 0 \
/kinetics/geometry cyan blue -15.034 -13.272 0
simundump kpool /kinetics/PKA/cAMP.R2C2 0 0 0 0 0 0 0 0 6e+05 0 \
/kinetics/geometry white blue -13.387 -18.855 0
simundump kpool /kinetics/PKA/cAMP2.R2C2 1 0 0 0 0 0 0 0 6e+05 0 \
/kinetics/geometry white blue -9.8392 -18.013 0
simundump kpool /kinetics/PKA/cAMP3.R2C2 1 0 0 0 0 0 0 0 6e+05 0 \
/kinetics/geometry white blue -7.1529 -19.073 0
simundump kpool /kinetics/PKA/cAMP4.R2C2 1 0 0 0 0 0 0 0 6e+05 0 \
/kinetics/geometry white blue -4.7663 -17.462 0
simundump kpool /kinetics/PKA/cAMP4.R2C 1 0 0 0 0 0 0 0 6e+05 0 \
/kinetics/geometry white blue -7.0495 -16.328 0
simundump kpool /kinetics/PKA/cAMP4.R2 1 0 0 0 0 0 0 0 6e+05 0 \
/kinetics/geometry white blue -13.387 -16.765 0
simundump kpool /kinetics/cAMP 1 0 0 0 0 0 0 0 6e+05 2 /kinetics/geometry \
green black -5.3828 -25.006 0
simundump kpool /kinetics/PKA-active 0 0 0 0 0 0 0 0 6e+05 0 \
/kinetics/geometry yellow black -6 -8 0
simundump doqcsinfo /kinetics/doqcsinfo 0 pdb135_1.g PKA pathway \
"Upinder S. Bhalla, NCBS" "Upinder S. Bhalla, NCBS" "citation here" \
"Generic Mammalian" "Brain - Neuronal" "Cell membrane + Cytosol" \
"Quantitative match to experiments, Quallitative" \
"Bhalla US Methods Enzymol. 2002;345:3-23 ( Peer-reviewed publication )" \
"Exact GENESIS implementation" "Approximates original data " -9 -6 0
simundump xgraph /graphs/conc1 0 0 1000 0 1 0
simundump xgraph /graphs/conc2 0 0 1000 0 1 0
simundump xplot /graphs/conc1/inhibited-PKA.Co 3 524288 \
"delete_plot.w ; edit_plot.D " cyan 0 0 1
simundump xplot /graphs/conc1/PKA-inhibitor.Co 3 524288 \
"delete_plot.w ; edit_plot.D " cyan 0 0 1
simundump xplot /graphs/conc2/cAMP.Co 3 524288 \
"delete_plot.w ; edit_plot.D " green 0 0 1
simundump xplot /graphs/conc2/PKA-active.Co 3 524288 \
"delete_plot.w ; edit_plot.D " yellow 0 0 1
simundump xgraph /moregraphs/conc3 0 0 100 0 1 0
simundump xgraph /moregraphs/conc4 0 0 100 0 1 0
simundump xcoredraw /edit/draw 0 -18.348 -2 -27.006 -5
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 \
"Derived from pka21.g," \
"identical except for renaming," \
"cleanups and getting rid of a " \
"couple of unused enzyme sites of" \
"PKA"
addmsg /kinetics/PKA/cAMP-bind-site-B1 /kinetics/PKA/R2C2 REAC A B
addmsg /kinetics/PKA/R2C2 /kinetics/PKA/cAMP-bind-site-B1 SUBSTRATE n
addmsg /kinetics/PKA/cAMP.R2C2 /kinetics/PKA/cAMP-bind-site-B1 PRODUCT n
addmsg /kinetics/cAMP /kinetics/PKA/cAMP-bind-site-B1 SUBSTRATE n
addmsg /kinetics/PKA/cAMP.R2C2 /kinetics/PKA/cAMP-bind-site-B2 SUBSTRATE n
addmsg /kinetics/cAMP /kinetics/PKA/cAMP-bind-site-B2 SUBSTRATE n
addmsg /kinetics/PKA/cAMP2.R2C2 /kinetics/PKA/cAMP-bind-site-B2 PRODUCT n
addmsg /kinetics/PKA/cAMP2.R2C2 /kinetics/PKA/cAMP-bind-site-A1 SUBSTRATE n
addmsg /kinetics/cAMP /kinetics/PKA/cAMP-bind-site-A1 SUBSTRATE n
addmsg /kinetics/PKA/cAMP3.R2C2 /kinetics/PKA/cAMP-bind-site-A1 PRODUCT n
addmsg /kinetics/cAMP /kinetics/PKA/cAMP-bind-site-A2 SUBSTRATE n
addmsg /kinetics/PKA/cAMP3.R2C2 /kinetics/PKA/cAMP-bind-site-A2 SUBSTRATE n
addmsg /kinetics/PKA/cAMP4.R2C2 /kinetics/PKA/cAMP-bind-site-A2 PRODUCT n
addmsg /kinetics/PKA/cAMP4.R2C2 /kinetics/PKA/Release-C1 SUBSTRATE n
addmsg /kinetics/PKA-active /kinetics/PKA/Release-C1 PRODUCT n
addmsg /kinetics/PKA/cAMP4.R2C /kinetics/PKA/Release-C1 PRODUCT n
addmsg /kinetics/PKA/cAMP4.R2C /kinetics/PKA/Release-C2 SUBSTRATE n
addmsg /kinetics/PKA-active /kinetics/PKA/Release-C2 PRODUCT n
addmsg /kinetics/PKA/cAMP4.R2 /kinetics/PKA/Release-C2 PRODUCT n
addmsg /kinetics/PKA/inhib-PKA /kinetics/PKA/PKA-inhibitor REAC A B
addmsg /kinetics/PKA-active /kinetics/PKA/inhib-PKA SUBSTRATE n
addmsg /kinetics/PKA/PKA-inhibitor /kinetics/PKA/inhib-PKA SUBSTRATE n
addmsg /kinetics/PKA/inhibited-PKA /kinetics/PKA/inhib-PKA PRODUCT n
addmsg /kinetics/PKA/inhib-PKA /kinetics/PKA/inhibited-PKA REAC B A
addmsg /kinetics/PKA/cAMP-bind-site-B1 /kinetics/PKA/cAMP.R2C2 REAC B A
addmsg /kinetics/PKA/cAMP-bind-site-B2 /kinetics/PKA/cAMP.R2C2 REAC A B
addmsg /kinetics/PKA/cAMP-bind-site-B2 /kinetics/PKA/cAMP2.R2C2 REAC B A
addmsg /kinetics/PKA/cAMP-bind-site-A1 /kinetics/PKA/cAMP2.R2C2 REAC A B
addmsg /kinetics/PKA/cAMP-bind-site-A1 /kinetics/PKA/cAMP3.R2C2 REAC B A
addmsg /kinetics/PKA/cAMP-bind-site-A2 /kinetics/PKA/cAMP3.R2C2 REAC A B
addmsg /kinetics/PKA/cAMP-bind-site-A2 /kinetics/PKA/cAMP4.R2C2 REAC B A
addmsg /kinetics/PKA/Release-C1 /kinetics/PKA/cAMP4.R2C2 REAC A B
addmsg /kinetics/PKA/Release-C1 /kinetics/PKA/cAMP4.R2C REAC B A
addmsg /kinetics/PKA/Release-C2 /kinetics/PKA/cAMP4.R2C REAC A B
addmsg /kinetics/PKA/Release-C2 /kinetics/PKA/cAMP4.R2 REAC B A
addmsg /kinetics/PKA/cAMP-bind-site-B1 /kinetics/cAMP REAC A B
addmsg /kinetics/PKA/cAMP-bind-site-B2 /kinetics/cAMP REAC A B
addmsg /kinetics/PKA/cAMP-bind-site-A1 /kinetics/cAMP REAC A B
addmsg /kinetics/PKA/cAMP-bind-site-A2 /kinetics/cAMP REAC A B
addmsg /kinetics/PKA/Release-C1 /kinetics/PKA-active REAC B A
addmsg /kinetics/PKA/Release-C2 /kinetics/PKA-active REAC B A
addmsg /kinetics/PKA/inhib-PKA /kinetics/PKA-active REAC A B
addmsg /kinetics/PKA/inhibited-PKA /graphs/conc1/inhibited-PKA.Co PLOT Co *inhibited-PKA.Co *cyan
addmsg /kinetics/PKA/PKA-inhibitor /graphs/conc1/PKA-inhibitor.Co PLOT Co *PKA-inhibitor.Co *cyan
addmsg /kinetics/cAMP /graphs/conc2/cAMP.Co PLOT Co *cAMP.Co *green
addmsg /kinetics/PKA-active /graphs/conc2/PKA-active.Co PLOT Co *PKA-active.Co *yellow
enddump
// End of dump
call /kinetics/PKA/notes LOAD \
"General ref: Taylor et al Ann Rev Biochem 1990 59:971-1005" \
""
call /kinetics/PKA/R2C2/notes LOAD \
"This is the R2C2 complex, consisting of 2 catalytic (C)" \
"subunits, and the R-dimer. See Taylor et al Ann Rev Biochem" \
"1990 59:971-1005 for a review." \
"The Doskeland and Ogreid review is better for numbers." \
"Amount of PKA is about .5 uM."
call /kinetics/PKA/cAMP-bind-site-B1/notes LOAD \
"Hasler et al FASEB J 6:2734-2741 1992 say Kd =1e-7M" \
"for type II, 5.6e-8 M for type I. Take mean" \
"which comes to 2e-13 #/cell" \
"Smith et al PNAS USA 78:3 1591-1595 1981 have better data." \
"First kf/kb=2.1e7/M = 3.5e-5 (#/cell)." \
"Ogreid and Doskeland Febs Lett 129:2 287-292 1981 have figs" \
"suggesting time course of complete assoc is < 1 min."
call /kinetics/PKA/cAMP-bind-site-B2/notes LOAD \
"For now let us set this to the same Km (1e-7M) as" \
"site B. This gives kf/kb = .7e-7M * 1e6 / (6e5^2) : 1/(6e5^2)" \
"= 2e-13:2.77e-12" \
"Smith et al have better values. They say that this is" \
"cooperative, so the consts are now kf/kb =8.3e-4"
call /kinetics/PKA/Release-C1/notes LOAD \
"This has to be fast, as the activation of PKA by cAMP" \
"is also fast." \
"kf was 10" \
""
call /kinetics/PKA/PKA-inhibitor/notes LOAD \
"About 25% of PKA C subunit is dissociated in resting cells without" \
"having any noticable activity." \
"Doskeland and Ogreid Int J biochem 13 pp1-19 suggest that this is" \
"because there is a corresponding amount of inhibitor protein."
call /kinetics/PKA/inhib-PKA/notes LOAD \
"This has to be set to zero for matching the expts in vitro." \
"In vivo we need to consider the inhibition though." \
"" \
""
call /kinetics/PKA/cAMP.R2C2/notes LOAD \
"CoInit was .0624" \
""
call /kinetics/PKA/cAMP4.R2/notes LOAD \
"Starts at 0.15 for the test of fig 6 in Smith et al, but we aren't using" \
"that paper any more."
call /kinetics/cAMP/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 cAMP-dependent " \
"rates in the PKA model to reflect this."
call /kinetics/PKA-active/notes LOAD \
"Conc of PKA in brain is about 1 uM"
call /kinetics/doqcsinfo/notes LOAD \
" General ref: Taylor et al Ann Rev Biochem 1990 59:971-1005"
complete_loading