// DOQCS : http://doqcs.ncbs.res.in/
// Accession Name = CondorelliGC
// Accession Number = 19
// Transcriber = Sudhir Sivakumaran, NCBS
// Developer = Condorelli P and George SC.
// Species = Generic mammalian
// Tissue = Pulmonary and vascular smooth muscle
// Cell Compartment = Cytosol
// Notes = This model features the observations of Condorelli P, George SC. Biophys J. (2001) 80(5):2110-9. They propose a in vivo mechanism for the binding of free NO to sGC based on in vitro data within both pulmonary and vascular smooth muscle. All the parameters used have been obtained from reported results based on experiments. One important conclusion they make is that control of sGC in vivo is most likely to be ultra-sensitive and that activation in vivo occurs at lower NO concentrations than previously reported.
//genesis
// kkit Version 11 flat dumpfile
// Saved on Thu Dec 8 14:50:38 2005
include kkit {argv 1}
FASTDT = 1e-05
SIMDT = 0.001
CONTROLDT = 1
PLOTDT = 0.1
MAXTIME = 1000
TRANSIENT_TIME = 5
VARIABLE_DT_FLAG = 1
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 1.6667e-21 3 sphere "" white black 0 \
-2 0
simundump doqcsinfo /kinetics/doqcsinfo 0 db19.g CondorelliGC pathway \
"Sudhir Sivakumaran, NCBS" "Condorelli P and George SC" "citation here" \
"Generic Mammalian" "Pulmonary and vascular smooth muscle" Cytosol \
"Quantitative match to experiments" \
"Condorelli P, George SC. Biophys J. (2001) 80(5):2110-9( Peer-reviewed publication )" \
"Mathematically equivalent" \
"Approximates original data , Quantitatively predicts new data" 0 0 0
simundump group /kinetics/GC 0 62 black x 0 0 "" GC \
/home2/bhalla/scripts/modules/GC_0.g 0 0 1 -5 -9 0
simundump kpool /kinetics/GC/NO_sGCpart_act 0 0 0 0 0 0 0 0 1 0 \
/kinetics/geometry 23 62 -15 -1 0
simundump kreac /kinetics/GC/NObind_sGC 0 980 350 "" white 62 -9 -2 0
simundump kreac /kinetics/GC/NOdepPway 0 1.68 0 "" white 62 -17 -4 0
simundump kreac /kinetics/GC/NOindePway 0 0.0609 0.014 "" white 62 -13 -4 0
simundump kpool /kinetics/GC/NO_sGCfull_act 0 0 0 0 0 0 0 0 1 0 \
/kinetics/geometry 7 62 -15 -7 0
simundump kenz /kinetics/GC/NO_sGCfull_act/full_act_sGC 0 0 0 0 0 1 3.4483 \
160 40 0 0 "" red 7 "" -15 -8 0
simundump kpool /kinetics/GC/GTP 0 0 1000 1000 1000 1000 0 0 1 0 \
/kinetics/geometry 54 62 -18 -11 0
simundump kpool /kinetics/GC/cGMP 0 0 0 0 0 0 0 0 1 0 /kinetics/geometry 14 \
62 -12 -11 0
simundump kpool /kinetics/GC/NO_a 0 0 0.1 0.1 0.1 0.1 0 0 1 0 \
/kinetics/geometry 47 62 -19 -1 0
simundump kpool /kinetics/GC/sGC_basal 0 0 3 3 3 3 0 0 1 0 /kinetics/geometry \
0 62 -11 -5 0
simundump kreac /kinetics/GC/dissoNO 0 0.07 0 "" white 62 -9 -8 0
simundump kpool /kinetics/GC/NO 0 0 0 0 0 0 0 0 1 0 /kinetics/geometry 4 62 \
-7 -5 0
simundump xgraph /graphs/conc1 0 0 547.8 0 0.29425 0
simundump xgraph /graphs/conc2 0 0 564.3 2.5659 3 0
simundump xplot /graphs/conc1/NO_sGCpart_act.Co 3 524288 \
"delete_plot.w ; edit_plot.D " 23 0 0 1
simundump xplot /graphs/conc1/NO_sGCfull_act.Co 3 524288 \
"delete_plot.w ; edit_plot.D " 7 0 0 1
simundump xplot /graphs/conc2/sGC_basal.Co 3 524288 \
"delete_plot.w ; edit_plot.D " 0 0 0 1
simundump xgraph /moregraphs/conc3 0 0 582.6 0 1000.1 0
simundump xgraph /moregraphs/conc4 0 0 575 0 0.1 0
simundump xplot /moregraphs/conc3/cGMP.Co 3 524288 \
"delete_plot.w ; edit_plot.D " 14 0 0 1
simundump xplot /moregraphs/conc4/NO_a.Co 3 524288 \
"delete_plot.w ; edit_plot.D " 47 0 0 1
simundump xcoredraw /edit/draw 0 -21 2 -13 2
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 \
"The model with the partial and fully active enzyme sGC as proposed by Condorelli et al. with NO activating sGC," \
"in a mechanism as proposed by Condorelli et al., 2001, Biophys J, 80:2110-2119...." \
"This is similar to condorelli_GCmodel_incNOS_Iwan.g, but the rates used here have been converted by 7X, since the" \
"original rates were obtained from experiments performed at 4C .... and the NOS reaction scheme is not included..."
addmsg /kinetics/GC/NObind_sGC /kinetics/GC/NO_sGCpart_act REAC B A
addmsg /kinetics/GC/NOindePway /kinetics/GC/NO_sGCpart_act REAC A B
addmsg /kinetics/GC/NOdepPway /kinetics/GC/NO_sGCpart_act REAC A B
addmsg /kinetics/GC/sGC_basal /kinetics/GC/NObind_sGC SUBSTRATE n
addmsg /kinetics/GC/NO_sGCpart_act /kinetics/GC/NObind_sGC PRODUCT n
addmsg /kinetics/GC/NO /kinetics/GC/NObind_sGC SUBSTRATE n
addmsg /kinetics/GC/NO_sGCpart_act /kinetics/GC/NOdepPway SUBSTRATE n
addmsg /kinetics/GC/NO_a /kinetics/GC/NOdepPway SUBSTRATE n
addmsg /kinetics/GC/NO_sGCfull_act /kinetics/GC/NOdepPway PRODUCT n
addmsg /kinetics/GC/NO_sGCpart_act /kinetics/GC/NOindePway SUBSTRATE n
addmsg /kinetics/GC/NO_sGCfull_act /kinetics/GC/NOindePway PRODUCT n
addmsg /kinetics/GC/NOindePway /kinetics/GC/NO_sGCfull_act REAC B A
addmsg /kinetics/GC/NOdepPway /kinetics/GC/NO_sGCfull_act REAC B A
addmsg /kinetics/GC/NO_sGCfull_act/full_act_sGC /kinetics/GC/NO_sGCfull_act REAC eA B
addmsg /kinetics/GC/dissoNO /kinetics/GC/NO_sGCfull_act REAC A B
addmsg /kinetics/GC/NO_sGCfull_act /kinetics/GC/NO_sGCfull_act/full_act_sGC ENZYME n
addmsg /kinetics/GC/GTP /kinetics/GC/NO_sGCfull_act/full_act_sGC SUBSTRATE n
addmsg /kinetics/GC/NO_sGCfull_act/full_act_sGC /kinetics/GC/GTP REAC sA B
addmsg /kinetics/GC/NO_sGCfull_act/full_act_sGC /kinetics/GC/cGMP MM_PRD pA
addmsg /kinetics/GC/NOdepPway /kinetics/GC/NO_a REAC A B
addmsg /kinetics/GC/NObind_sGC /kinetics/GC/sGC_basal REAC A B
addmsg /kinetics/GC/dissoNO /kinetics/GC/sGC_basal REAC B A
addmsg /kinetics/GC/NO_sGCfull_act /kinetics/GC/dissoNO SUBSTRATE n
addmsg /kinetics/GC/NO /kinetics/GC/dissoNO PRODUCT n
addmsg /kinetics/GC/sGC_basal /kinetics/GC/dissoNO PRODUCT n
addmsg /kinetics/GC/NObind_sGC /kinetics/GC/NO REAC A B
addmsg /kinetics/GC/dissoNO /kinetics/GC/NO REAC B A
addmsg /kinetics/GC/NO_sGCpart_act /graphs/conc1/NO_sGCpart_act.Co PLOT Co *NO_sGCpart_act.Co *23
addmsg /kinetics/GC/NO_sGCfull_act /graphs/conc1/NO_sGCfull_act.Co PLOT Co *NO_sGCfull_act.Co *7
addmsg /kinetics/GC/sGC_basal /graphs/conc2/sGC_basal.Co PLOT Co *sGC_basal.Co *0
addmsg /kinetics/GC/cGMP /moregraphs/conc3/cGMP.Co PLOT Co *cGMP.Co *14
addmsg /kinetics/GC/NO_a /moregraphs/conc4/NO_a.Co PLOT Co *NO_a.Co *47
enddump
// End of dump
call /kinetics/doqcsinfo/notes LOAD \
"This model features the observations of Condorelli P, George SC. Biophys J. (2001) 80(5):2110-9. They propose a in vivo mechanism for the binding of free NO to sGC based on in vitro data within both pulmonary and vascular smooth muscle. All the parameters used have been obtained from reported results based on experiments. One important conclusion they make is that control of sGC in vivo is most likely to be ultra-sensitive and that activation in vivo occurs at lower NO concentrations than previously reported."
call /kinetics/GC/NO_sGCpart_act/notes LOAD \
"This is the partiallly active form of sGC bound with NO, as " \
"proposed by Condorelli et al., 2001, Biophys J, 80:2110-2119.." \
"based originally on Zhao et al., 1999, PNAS,96:14753-14758."
call /kinetics/GC/NObind_sGC/notes LOAD \
"Rates at 4C..." \
"used directly from paper by Condorelli P, 2001, Biophysical J," \
"80:2110-2119, which in turn have been obtained mainly from" \
"Zhao et al., 1999, PNAS,96:14753-14758."
call /kinetics/GC/NOdepPway/notes LOAD \
"Rates from stopped flow experiments performed at 4C from" \
"Zhao et al., 1999, PNAS,96:14753-14758." \
"" \
"Same rates used by Condorelli P, for his simulations..."
call /kinetics/GC/NOindePway/notes LOAD \
"Rates used directly from Condorelli et al., 2001, Biophysical J," \
"80:2110-2119 ...." \
"Rates originally from Zhao et al., 1999, PNAS, 96:14753-14758" \
"from stopped flow spectroscopy experiments performed at 4C."
call /kinetics/GC/NO_sGCfull_act/notes LOAD \
"This is the fully active form of sGC, catalysing the conversion " \
"of GTP to cGMP....as proposed by Condorelli et al., 2001, " \
"Biophys J, 80:14753-14758." \
""
call /kinetics/GC/NO_sGCfull_act/full_act_sGC/notes LOAD \
"Km values for the basal and fully activated forms of sGC have" \
"been determined as 85-120 uM and 58 uM, respectively ..." \
"(Ignarro et al., 1982, BBA, 718:49-59)..and the same has been" \
"used by Condorelli et al., 2001..." \
"" \
"Vmax values are around 10-100 nmol/min/mg (without NO) and" \
"10-40 umol/min/mg (with NO) ..... thru personal correspondence" \
"with T Bellamy, UK. "
call /kinetics/GC/GTP/notes LOAD \
"Under in vivo conditions, GTP is present in excess, ~ 1 mM." \
""
call /kinetics/GC/sGC_basal/notes LOAD \
"Intracellular levels of sGC is around 3 uM, as sGC is enriched" \
"in Purkinje cells. (Shinya Kuroda, personal correpondence)..."
call /kinetics/GC/dissoNO/notes LOAD \
"This is a modification by Condorelli et al., 2001, Biophys J" \
"of the recent binding scheme of Zhao et al., to include the" \
"NO dissociation from fully active complex of sGC..." \
"" \
"The dissociation is characterised by the respective first order" \
"rate constants depicted in the model... Rates are obtained at " \
"4C..."
call /kinetics/GC/NO/notes LOAD \
"Endogenously produced NO concentrations in the course of" \
"signal transduction processes are < 100 nM. (Varner et al.," \
"Nitric oxide in the nervous system, Academic press, London, UK," \
"pp.191-206.)"
complete_loading