// DOQCS : http://doqcs.ncbs.res.in/ // Accession Name = CDK2-CyclinA_activation_pathway // Accession Number = 42 // 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 = In this version of the CDK2/Cyclin A complex activation there is discrepancy in the first curve which plots the binding reaction of CDK2 and Cyclin A expressed in E. coli. With the published rate constants the simulation does not match the published graph (Fig.1B) in Morris MC. et al. J Biol Chem. (2002) 277(26):23847-53. //genesis // kkit Version 11 flat dumpfile // Saved on Thu Dec 8 15:54:03 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 \ -14 1 0 simundump geometry /kinetics/geometry[1] 0 7.2e-17 3 sphere "" white black \ -11 1 0 simundump kpool /kinetics/CDK2cycA 0 0 0 0 0 0 0 0 5.9999e+05 0 \ /kinetics/geometry 36 black -16 -5 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 -9 0 simundump kpool /kinetics/Cdk2 0 0 0.1 0.1 59999 59999 0 0 5.9999e+05 0 \ /kinetics/geometry 54 black -20 -5 0 simundump kpool /kinetics/CDK2cycA* 0 0 0 0 0 0 0 0 5.9999e+05 0 \ /kinetics/geometry 62 black -12 -5 0 simundump kreac /kinetics/Binding 0 3.1667e-05 25 "" 1 black -18 -7 0 simundump kreac /kinetics/Activation 0 0.813 0.557 "" 0 black -14 -7 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 -3 0 simundump kpool /kinetics/basal_fluorescence 0 0 1.2121 1.2121 52363 52363 0 \ 0 43200 0 /kinetics/geometry[1] 48 black -16 -1 0 simundump doqcsinfo /kinetics/doqcsinfo 0 db42.g \ CDK2-CyclinA_activation_pathway 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 Qualitative \ In-house "Exact GENESIS implementation" "Approximates original data " -12 2 \ 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 -9 -11 4 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 \ "Uses rate constants from " \ "Morris et al 2002" \ "JBC 277(26): 23847--23853" \ "There is a discrepancy on the first curve (the inset of Fig.1B)" \ "" 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 = 19/sec/uM and kb = 25/sec " \ "Morris et al 2002" \ "JBC 277(26): 23847--23853" \ "Table 1 pp.23849" 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=0.813/sec and kb=0.557/sec used in 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 \ "In this version of the CDK2/Cyclin A complex activation there is discrepancy in the first curve which plots the binding reaction of CDK2 and Cyclin A expressed in E. coli. With the published rate constants the simulation does not match the published graph (Fig.1B) in Morris MC. et al. J Biol Chem. (2002) 277(26):23847-53." complete_loading