//  DOQCS : http://doqcs.ncbs.res.in/ 
//  Accession Name = Stuehr_NOS 
//  Accession Number = 12 
//  Transcriber = Sudhir Sivakumaran, NCBS 
//  Developer = Santolini, Adak, Curran, Stuehr 
//  Species = Generic mammalian 
//  Tissue = Neuronal ; Expressioned in E.coli 
//  Cell Compartment = Cytosol 
//  Notes =  This is a model of neuronal Nitric Oxide Synthase expressed in Escherichia coli based on <a href= http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11038356 > Santolini J. et al.  J Biol Chem. (2001) 276(2):1233-43</a>. The rates have been converted by 2x for every 10 degrees C. The original temperature was 10 degree C, cell temperature is assumed 30 degree C, so the conversion factor is 4. 
 
 //genesis
// kkit Version 11 flat dumpfile
 
// Saved on Thu Dec  8 14:09:11 2005
 
include kkit {argv 1}
 
FASTDT = 1e-05
SIMDT = 0.001
CONTROLDT = 1
PLOTDT = 0.1
MAXTIME = 600
TRANSIENT_TIME = 10
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 \
  -25 -29 0
simundump group /kinetics/NOS 0 yellow black x 0 0 "" NOS \
  /home2/bhalla/scripts/modules/NOS_0.g 0 0 0 -30 -34 0
simundump kreac /kinetics/NOS/k3 0 104 0 "" white yellow -41 -28 0
simundump kreac /kinetics/NOS/k6 0 104 0 "" white yellow -41 -30 0
simundump kreac /kinetics/NOS/k5 0 3.6 0 "" white yellow -43 -32 0
simundump kpool /kinetics/NOS/FeIII_NO 0 0 0 0 0 0 0 0 1 0 /kinetics/geometry \
  42 yellow -39 -34 0
simundump kpool /kinetics/NOS/FeII-O2_a 0 0 0 0 0 0 0 0 1 0 \
  /kinetics/geometry 1 yellow -41 -34 0
simundump kpool /kinetics/NOS/FeII_a 0 0 0 0 0 0 0 0 1 0 /kinetics/geometry \
  26 yellow -43 -29 0
simundump kpool /kinetics/NOS/FeIII_a 0 0 0 0 0 0 0 0 1 0 /kinetics/geometry \
  51 yellow -41 -25 0
simundump kpool /kinetics/NOS/CaM-Ca4 1 0 0 0 0 0 0 0 1 0 /kinetics/geometry \
  blue yellow -30 -19 0
simundump kpool /kinetics/NOS/L-Arg 0 0 100 100 100 100 0 0 1 0 \
  /kinetics/geometry 9 yellow -33 -22 0
simundump kpool /kinetics/NOS/FeIII 0 0 0 0 0 0 0 0 1 0 /kinetics/geometry 57 \
  yellow -35 -25 0
simundump kpool /kinetics/NOS/FeII 0 0 0 0 0 0 0 0 1 0 /kinetics/geometry 22 \
  yellow -37 -25 0
simundump kpool /kinetics/NOS/FeII-O2 0 0 0 0 0 0 0 0 1 0 /kinetics/geometry \
  29 yellow -39 -25 0
simundump kpool /kinetics/NOS/nNOS 0 0 10 10 10 10 0 0 1 0 /kinetics/geometry \
  27 yellow -30 -30 0
simundump kreac /kinetics/NOS/Ca-CaMbind-nNOS 0 3.25 0.05 "" white yellow -30 \
  -23 0
simundump kpool /kinetics/NOS/Ca-CaM_nNOS 0 0 0 0 0 0 0 0 1 0 \
  /kinetics/geometry 33 yellow -31 -27 0
simundump kreac /kinetics/NOS/arg_bind_nNOS 0 0.5 81 "" white yellow -33 -25 \
  0
simundump kpool /kinetics/NOS/O2 0 0 0.5 0.5 0.5 0.5 0 0 1 0 \
  /kinetics/geometry 4 yellow -33 -27 0
simundump kpool /kinetics/NOS/NO3 0 0 0 0 0 0 0 0 1 0 /kinetics/geometry 56 \
  yellow -34 -34 0
simundump kpool /kinetics/NOS/FeII_NO 0 0 0 0 0 0 0 0 1 0 /kinetics/geometry \
  62 yellow -36 -34 0
simundump kreac /kinetics/NOS/k2 0 3.6 0 "" white yellow -39 -28 0
simundump kreac /kinetics/NOS/k1 0 10.4 0 "" white yellow -37 -28 0
simundump kreac /kinetics/NOS/kF 0 20 0 "" white yellow -35 -28 0
simundump kreac /kinetics/NOS/kG 0 10.4 0 "" white yellow -39 -30 0
simundump kreac /kinetics/NOS/k9 0 0.0004 0 "" white yellow -36 -30 0
simundump kreac /kinetics/NOS/k10 0 1.2 0 "" white yellow -34 -30 0
simundump kreac /kinetics/NOS/k4 0 10.4 0 "" white yellow -43 -26 0
simundump doqcsinfo /kinetics/doqcsinfo 0 db12.g Stuehr_NOS pathway \
  "Sudhir Sivakumaran, NCBS" "Santolini, Adak, Curran, Stuehr" \
  "citation here" "Generic Mammalian" "Neuronal ; Expressioned in E.coli" \
  Cytosol "Quantitative match to experiments" \
  "<a href = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11038356> Santolini J. et al. J Biol Chem. (2001) 276(2):1233-43</a> ( Peer-reviewed publication )" \
  "Approximate implementation" "Approximates original data " -24 -26 0
simundump xgraph /graphs/conc1 0 0 600 0 0.68446 1
simundump xgraph /graphs/conc2 0 0 600 0 0.02648 1
simundump xplot /graphs/conc1/FeIII_NO.Co 3 524288 \
  "delete_plot.w <s> <d>; edit_plot.D <w>" 42 0 0 1
simundump xplot /graphs/conc1/Ca-CaM.Co 3 524288 \
  "delete_plot.w <s> <d>; edit_plot.D <w>" 57 0 0 1
simundump xplot /graphs/conc1/FeII_NO.Co 3 524288 \
  "delete_plot.w <s> <d>; edit_plot.D <w>" 62 0 0 1
simundump xplot /graphs/conc2/FeIII.Co 3 524288 \
  "delete_plot.w <s> <d>; edit_plot.D <w>" 57 0 0 1
simundump xplot /graphs/conc2/FeII.Co 3 524288 \
  "delete_plot.w <s> <d>; edit_plot.D <w>" 22 0 0 1
simundump xplot /graphs/conc2/CaM-Ca4.Co 3 524288 \
  "delete_plot.w <s> <d>; edit_plot.D <w>" blue 0 0 1
simundump xgraph /moregraphs/conc3 0 0 600 0 0.026471 1
simundump xgraph /moregraphs/conc4 0 0 600 0 0.50003 1
simundump xplot /moregraphs/conc3/FeII-O2_a.Co 3 524288 \
  "delete_plot.w <s> <d>; edit_plot.D <w>" 1 0 0 1
simundump xplot /moregraphs/conc3/FeII_a.Co 3 524288 \
  "delete_plot.w <s> <d>; edit_plot.D <w>" 26 0 0 1
simundump xplot /moregraphs/conc3/FeIII_a.Co 3 524288 \
  "delete_plot.w <s> <d>; edit_plot.D <w>" 51 0 0 1
simundump xplot /moregraphs/conc4/FeII-O2.Co 3 524288 \
  "delete_plot.w <s> <d>; edit_plot.D <w>" 29 0 0 1
simundump xplot /moregraphs/conc4/NO3.Co 3 524288 \
  "delete_plot.w <s> <d>; edit_plot.D <w>" 56 0 0 1
simundump xcoredraw /edit/draw 0 -45 -13 -36 -17
simundump xtree /edit/draw/tree 0 \
  /kinetics/#[],/kinetics/#[]/#[],/kinetics/#[]/#[]/#[][TYPE!=proto],/kinetics/#[]/#[]/#[][TYPE!=linkinfo]/##[] \
  "edit_elm.D <v>; drag_from_edit.w <d> <S> <x> <y> <z>" auto 0.6
simundump xtext /file/notes 0 1
xtextload /file/notes \
"NO synthesis by NOS (nNOS) in the mammalian brain." \
"model based on Stuehr et al., JBC, 2001;276(2):1233-1243." \
"Rates used from the literature, increased by 2X for every 10 C rise," \
"to get the rates at the cell temperature. " \
"" \
"" \
"Incorporated basal dephosph of " \
"neurogranin which gives around 20%" \
"phosph at basal PKC activity." \
"Deleted CONSERVE msg from Ca to" \
"itself."
addmsg /kinetics/NOS/FeII-O2 /kinetics/NOS/k3 SUBSTRATE n 
addmsg /kinetics/NOS/FeIII_a /kinetics/NOS/k3 PRODUCT n 
addmsg /kinetics/NOS/FeII-O2_a /kinetics/NOS/k6 SUBSTRATE n 
addmsg /kinetics/NOS/FeIII_NO /kinetics/NOS/k6 PRODUCT n 
addmsg /kinetics/NOS/FeII_a /kinetics/NOS/k5 SUBSTRATE n 
addmsg /kinetics/NOS/FeII-O2_a /kinetics/NOS/k5 PRODUCT n 
addmsg /kinetics/NOS/k6 /kinetics/NOS/FeIII_NO REAC B A 
addmsg /kinetics/NOS/kG /kinetics/NOS/FeIII_NO REAC A B 
addmsg /kinetics/NOS/kF /kinetics/NOS/FeIII_NO REAC A B 
addmsg /kinetics/NOS/k5 /kinetics/NOS/FeII-O2_a REAC B A 
addmsg /kinetics/NOS/k6 /kinetics/NOS/FeII-O2_a REAC A B 
addmsg /kinetics/NOS/k4 /kinetics/NOS/FeII_a REAC B A 
addmsg /kinetics/NOS/k5 /kinetics/NOS/FeII_a REAC A B 
addmsg /kinetics/NOS/k3 /kinetics/NOS/FeIII_a REAC B A 
addmsg /kinetics/NOS/k4 /kinetics/NOS/FeIII_a REAC A B 
addmsg /kinetics/NOS/Ca-CaMbind-nNOS /kinetics/NOS/CaM-Ca4 REAC A B 
addmsg /kinetics/NOS/arg_bind_nNOS /kinetics/NOS/L-Arg REAC A B 
addmsg /kinetics/NOS/k1 /kinetics/NOS/FeIII REAC A B 
addmsg /kinetics/NOS/k10 /kinetics/NOS/FeIII REAC B A 
addmsg /kinetics/NOS/kF /kinetics/NOS/FeIII REAC B A 
addmsg /kinetics/NOS/arg_bind_nNOS /kinetics/NOS/FeIII REAC B A 
addmsg /kinetics/NOS/k1 /kinetics/NOS/FeII REAC B A 
addmsg /kinetics/NOS/k2 /kinetics/NOS/FeII REAC A B 
addmsg /kinetics/NOS/k9 /kinetics/NOS/FeII REAC B A 
addmsg /kinetics/NOS/k2 /kinetics/NOS/FeII-O2 REAC B A 
addmsg /kinetics/NOS/k3 /kinetics/NOS/FeII-O2 REAC A B 
addmsg /kinetics/NOS/Ca-CaMbind-nNOS /kinetics/NOS/nNOS REAC A B 
addmsg /kinetics/NOS/nNOS /kinetics/NOS/Ca-CaMbind-nNOS SUBSTRATE n 
addmsg /kinetics/NOS/CaM-Ca4 /kinetics/NOS/Ca-CaMbind-nNOS SUBSTRATE n 
addmsg /kinetics/NOS/Ca-CaM_nNOS /kinetics/NOS/Ca-CaMbind-nNOS PRODUCT n 
addmsg /kinetics/NOS/arg_bind_nNOS /kinetics/NOS/Ca-CaM_nNOS REAC A B 
addmsg /kinetics/NOS/Ca-CaMbind-nNOS /kinetics/NOS/Ca-CaM_nNOS REAC B A 
addmsg /kinetics/NOS/L-Arg /kinetics/NOS/arg_bind_nNOS SUBSTRATE n 
addmsg /kinetics/NOS/FeIII /kinetics/NOS/arg_bind_nNOS PRODUCT n 
addmsg /kinetics/NOS/Ca-CaM_nNOS /kinetics/NOS/arg_bind_nNOS SUBSTRATE n 
addmsg /kinetics/NOS/k10 /kinetics/NOS/O2 REAC A B 
addmsg /kinetics/NOS/k10 /kinetics/NOS/NO3 REAC B A 
addmsg /kinetics/NOS/kG /kinetics/NOS/FeII_NO REAC B A 
addmsg /kinetics/NOS/k9 /kinetics/NOS/FeII_NO REAC A B 
addmsg /kinetics/NOS/k10 /kinetics/NOS/FeII_NO REAC A B 
addmsg /kinetics/NOS/FeII /kinetics/NOS/k2 SUBSTRATE n 
addmsg /kinetics/NOS/FeII-O2 /kinetics/NOS/k2 PRODUCT n 
addmsg /kinetics/NOS/FeIII /kinetics/NOS/k1 SUBSTRATE n 
addmsg /kinetics/NOS/FeII /kinetics/NOS/k1 PRODUCT n 
addmsg /kinetics/NOS/FeIII_NO /kinetics/NOS/kF SUBSTRATE n 
addmsg /kinetics/NOS/FeIII /kinetics/NOS/kF PRODUCT n 
addmsg /kinetics/NOS/FeIII_NO /kinetics/NOS/kG SUBSTRATE n 
addmsg /kinetics/NOS/FeII_NO /kinetics/NOS/kG PRODUCT n 
addmsg /kinetics/NOS/FeII_NO /kinetics/NOS/k9 SUBSTRATE n 
addmsg /kinetics/NOS/FeII /kinetics/NOS/k9 PRODUCT n 
addmsg /kinetics/NOS/FeII_NO /kinetics/NOS/k10 SUBSTRATE n 
addmsg /kinetics/NOS/FeIII /kinetics/NOS/k10 PRODUCT n 
addmsg /kinetics/NOS/NO3 /kinetics/NOS/k10 PRODUCT n 
addmsg /kinetics/NOS/O2 /kinetics/NOS/k10 SUBSTRATE n 
addmsg /kinetics/NOS/FeIII_a /kinetics/NOS/k4 SUBSTRATE n 
addmsg /kinetics/NOS/FeII_a /kinetics/NOS/k4 PRODUCT n 
addmsg /kinetics/NOS/FeIII_NO /graphs/conc1/FeIII_NO.Co PLOT Co *FeIII_NO.Co *42 
addmsg /kinetics/NOS/CaM-Ca4 /graphs/conc1/Ca-CaM.Co PLOT Co *Ca-CaM.Co *57 
addmsg /kinetics/NOS/FeII_NO /graphs/conc1/FeII_NO.Co PLOT Co *FeII_NO.Co *62 
addmsg /kinetics/NOS/FeIII /graphs/conc2/FeIII.Co PLOT Co *FeIII.Co *57 
addmsg /kinetics/NOS/FeII /graphs/conc2/FeII.Co PLOT Co *FeII.Co *22 
addmsg /kinetics/NOS/CaM-Ca4 /graphs/conc2/CaM-Ca4.Co PLOT Co *CaM-Ca4.Co *blue 
addmsg /kinetics/NOS/FeII-O2_a /moregraphs/conc3/FeII-O2_a.Co PLOT Co *FeII-O2_a.Co *1 
addmsg /kinetics/NOS/FeII_a /moregraphs/conc3/FeII_a.Co PLOT Co *FeII_a.Co *26 
addmsg /kinetics/NOS/FeIII_a /moregraphs/conc3/FeIII_a.Co PLOT Co *FeIII_a.Co *51 
addmsg /kinetics/NOS/FeII-O2 /moregraphs/conc4/FeII-O2.Co PLOT Co *FeII-O2.Co *29 
addmsg /kinetics/NOS/NO3 /moregraphs/conc4/NO3.Co PLOT Co *NO3.Co *56 
enddump
// End of dump

call /kinetics/NOS/k3/notes LOAD \
"rates from Stuehr et al., 2001, JBC, 276(2):1233-1243" \
"" \
"rates increased by 2X for every 10 C rise, to get it ot the cell temp.." \
"(thru personal correspondence)" \
"" \
"kf -- 104"
call /kinetics/NOS/k6/notes LOAD \
"rates from Stuehr et al., 2001, JBC, 276(2): 1233-1243" \
"The transformation rate of FeII-O2_a to FeIII_NO was 26 /s." \
"rates increased by 2X for every 10 C to get it to the cell temp..." \
"(thru personal correspondence)" \
"" \
"kf -- 104" \
""
call /kinetics/NOS/k5/notes LOAD \
"rates from Stuehr et al., 2001, JBC, 276(2):1233-1243" \
"" \
"rates increased by 2X for every 10 C rise to get it to the cell temp.." \
"(thru personal correspondence)" \
"" \
"kf -- 3.6" \
""
call /kinetics/NOS/L-Arg/notes LOAD \
"The intracellular concentrations are atleast 100 uM."
call /kinetics/NOS/nNOS/notes LOAD \
"neuronal Nitric Oxide Synthase." \
"Found in neurons, activity dependent on CaM binding," \
"in response to Ca levels." \
"" \
"molecular weight ~160 kDa." \
""
call /kinetics/NOS/Ca-CaMbind-nNOS/notes LOAD \
"Those binding CaM have a high Kd, including nNOS, ~ <= 10 nM." \
"" \
"The binding of CaM to NOS has been demonstrated to act as the" \
"trigger necessary for electron transfer and catalytic " \
"activity." \
"(Marletta, Biochemistry, 1997;36;12337-12345)"
call /kinetics/NOS/arg_bind_nNOS/notes LOAD \
"" \
"from Stuehr et al., Biochem, 1999, 38(38):12446-12451." \
"Rates used as it is from their results."
call /kinetics/NOS/k2/notes LOAD \
"rates from Stuehr et al., 2001, JBC, 276(2):1233-1243" \
"" \
"rates increased by 2X for every 10 C rise, to get it ot the cell temp.." \
"(thru personal correspondence)" \
"" \
"kf -- 3.6" \
""
call /kinetics/NOS/k1/notes LOAD \
"rates from Stuehr et al., 2001, JBC, 276(2):1233-1243." \
"All the rates increased by 2X for every 10 C rise to get it to" \
"the cell temp.." \
"(thru personal correspondence)" \
"" \
"kf -- 10.4" \
""
call /kinetics/NOS/kF/notes LOAD \
"rates from Stuehr et al., JBC, 2001; 276(2): 1233-1243." \
"" \
"rates increased by 2X for every 10 C rise, to get it ot the cell temp.." \
"(thru personal correspondence)" \
"" \
"kf -- 20" \
""
call /kinetics/NOS/kG/notes LOAD \
"rates from Stuehr et al., 2001, JBC, 276(2): 1233-1243.." \
"" \
"rates increased by 2X for every 10 C rise, to get it to the cell temp.." \
"(thru personal correspondence)" \
"" \
"kf -- 10.4" \
""
call /kinetics/NOS/k9/notes LOAD \
"rates from Stuehr et al., 2001, JBC 276(2): 1233-1243.." \
"" \
"rates increased by 2X for every 10 C rise, to get it to the cell temp.." \
"(thru personal correspondence)" \
"" \
"kf -- 0.0004" \
""
call /kinetics/NOS/k10/notes LOAD \
"The rates were obtained from Stuehr et al, JBC 2001, 276(2):" \
"1233-1243...." \
"" \
"The rates are multiplied by 2X for every 10 C rise, to get it" \
"to the cell temp." \
"" \
"kf -- 0.0052" \
""
call /kinetics/NOS/k4/notes LOAD \
"rates from Stuehr et al., 2001, JBC, 276(2):1233-1243" \
"" \
"rates increased by 2X for every 10 C rise to get it to the cell temp.." \
"(thru personal correspondence)" \
"" \
"kf -- 10.4" \
""
call /kinetics/doqcsinfo/notes LOAD \
"This is a model of neuronal Nitric Oxide Synthase expressed in Escherichia coli based on <a href=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11038356> Santolini J. et al.  J Biol Chem. (2001) 276(2):1233-43</a>. The rates have been converted by 2x for every 10 degrees C. The original temperature was 10 degree C, cell temperature is assumed 30 degree C, so the conversion factor is 4."
complete_loading