// DOQCS : http://doqcs.ncbs.res.in/
// Accession Name = CDK2-CyclinA_activation_improved
// Accession Number = 43
// Transcriber = Sharat J. Vayttaden, NCBS
// Developer = May C. Morris, Claire Gondeau, John A. Tainer and Gilles Divita
// Species = Human, Xenopus
// Tissue = Expressed in E.coli
// Cell Compartment = Cytosol
// Notes = This version of the model for CDK2/Cyclin A complex activation (expressed in E. coli) is a good match to the data and the simulation matches the graphs Fig.1B and Fig.1B inset. The rate constants though differ from the rate constants in Morris MC. et al. J Biol Chem. (2002) 277(26):23847-53.
//genesis
// kkit Version 11 flat dumpfile
// Saved on Thu Dec 8 16:26:30 2005
include kkit {argv 1}
FASTDT = 0.0001
SIMDT = 0.0001
CONTROLDT = 0.001
PLOTDT = 0.001
MAXTIME = 12
TRANSIENT_TIME = 2
VARIABLE_DT_FLAG = 0
DEFAULT_VOL = 1e-15
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 9.9998e-16 3 sphere "" white black \
-10 0 0
simundump geometry /kinetics/geometry[1] 0 7.2e-17 3 sphere "" white black -7 \
0 0
simundump kpool /kinetics/CDK2cycA 0 0 0 0 0 0 0 0 5.9999e+05 0 \
/kinetics/geometry 36 black -16 -4 0
simundump kpool /kinetics/CyclinA 0 0 0.40001 0.40001 2.4e+05 2.4e+05 0 0 \
5.9999e+05 0 /kinetics/geometry 46 black -20 -8 0
simundump kpool /kinetics/Cdk2 0 0 0.1 0.1 59999 59999 0 0 5.9999e+05 0 \
/kinetics/geometry 54 black -20 -4 0
simundump kpool /kinetics/CDK2cycA* 0 0 0 0 0 0 0 0 5.9999e+05 0 \
/kinetics/geometry 62 black -12 -4 0
simundump kreac /kinetics/Binding 0 5.5001e-05 50 "" 1 black -18 -6 0
simundump kreac /kinetics/Activation 0 1.1 0.6 "" 0 black -14 -6 0
simundump kpool /kinetics/total_fluorescence 0 0 0.13889 1.2121 52363 5999.9 \
0 0 43200 0 /kinetics/geometry[1] 1 black -14 -2 0
simundump kpool /kinetics/basal_fluorescence 0 0 1.2121 1.2121 52363 52363 0 \
0 43200 0 /kinetics/geometry[1] 48 black -16 0 0
simundump doqcsinfo /kinetics/doqcsinfo 0 db43.g \
CDK2-CyclinA_activation_improved pathway "Sharat J. Vayttaden, NCBS" \
"May C. Morris, Claire Gondeau, John A. Tainer and Gilles Divita" \
"citation here" "Human, Xenopus" "Expressed in E.coli" Cytosol \
"Quantitative match to experiments" In-house "Exact GENESIS implementation" \
"Approximates original data " -10 1 0
simundump xgraph /graphs/conc1 0 0 12 1.2 1.8 0
simundump xgraph /graphs/conc2 0 0 12 1.2 1.8 0
simundump xplot /graphs/conc1/total_fluorescence.Co 3 524288 \
"delete_plot.w ; edit_plot.D " 1 0 0 1
simundump xgraph /moregraphs/conc3 0 0 12 1.2 1.8 0
simundump xgraph /moregraphs/conc4 0 0 12 1.2 1.8 0
simundump xcoredraw /edit/draw 0 -22 -2 -10 3
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 \
"This version is a good match to the data but differs" \
"from the rate constants from the paper." \
"Morris et al 2002" \
"JBC 277(26): 23847--23853"
addmsg /kinetics/Activation /kinetics/CDK2cycA REAC A B
addmsg /kinetics/Binding /kinetics/CDK2cycA REAC B A
addmsg /kinetics/Binding /kinetics/CyclinA REAC A B
addmsg /kinetics/Binding /kinetics/Cdk2 REAC A B
addmsg /kinetics/Activation /kinetics/CDK2cycA* REAC B A
addmsg /kinetics/Cdk2 /kinetics/Binding SUBSTRATE n
addmsg /kinetics/CyclinA /kinetics/Binding SUBSTRATE n
addmsg /kinetics/CDK2cycA /kinetics/Binding PRODUCT n
addmsg /kinetics/CDK2cycA /kinetics/Activation SUBSTRATE n
addmsg /kinetics/CDK2cycA* /kinetics/Activation PRODUCT n
addmsg /kinetics/CDK2cycA /kinetics/total_fluorescence SUMTOTAL n nInit
addmsg /kinetics/CDK2cycA* /kinetics/total_fluorescence SUMTOTAL n nInit
addmsg /kinetics/basal_fluorescence /kinetics/total_fluorescence SUMTOTAL n nInit
addmsg /kinetics/total_fluorescence /graphs/conc1/total_fluorescence.Co PLOT Co *total_fluorescence.Co *1
enddump
// End of dump
call /kinetics/CDK2cycA/notes LOAD \
"CoInit = 0 uM" \
"Morris et al 2002" \
"JBC 277(26): 23847--23853" \
"Reaction scheme 1 pp.23848"
call /kinetics/CyclinA/notes LOAD \
"CoInit = 0.4 uM" \
"Morris et al 2002" \
"JBC 277(26): 23847--23853" \
"Fig.1 pp.23848"
call /kinetics/Cdk2/notes LOAD \
"CoInit = 0.1uM " \
"Morris et al 2002" \
"JBC 277(26): 23847--23853" \
"Fig.1 pp.23848"
call /kinetics/CDK2cycA*/notes LOAD \
"CoInit = 0 uM" \
"Morris et al 2002" \
"JBC 277(26): 23847--23853" \
"Reaction scheme 1 pp.23848"
call /kinetics/Binding/notes LOAD \
"kf = 33/sec/uM and kb = 50/sec" \
"differs from the values in " \
"Morris et al 2002" \
"JBC 277(26): 23847--23853" \
"Table 1 pp.23849" \
"Published kf = 19/sec/uM and kb = 25/sec"
call /kinetics/Activation/notes LOAD \
"Morris et al 2002" \
"JBC 277(26): 23847--23853" \
"kf and kb values not published" \
"kobs2 = 2.5+-0.1/sec" \
"" \
"kf = 1.1/sec and kb = 0.6/sec used in this simulation"
call /kinetics/total_fluorescence/notes LOAD \
"The volume of this pool is scaled to 1/5.8 times the" \
"general volume in the model (1e-15 m^3) so that the" \
"range of fluorescent changes is 0.058 for complete" \
"consumption of the fluorophore (0.1 uM of Cdk2)." \
"The volume is therefore 0.1724e-15"
call /kinetics/basal_fluorescence/notes LOAD \
"Basal fluorescence is 1.2121" \
"Based on data points extracted from" \
"Morris et al 2002" \
"JBC 277(26): 23847--23853" \
"Fig.1B inset, page 23848"
call /kinetics/doqcsinfo/notes LOAD \
"This version of the model for CDK2/Cyclin A complex activation (expressed in E. coli) is a good match to the data and the simulation matches the graphs Fig.1B and Fig.1B inset. The rate constants though differ from the rate constants in Morris MC. et al. J Biol Chem. (2002) 277(26):23847-53"
complete_loading