//genesis // kkit Version 11 flat dumpfile // Saved on Fri May 12 21:12:12 2006 include kkit {argv 1} FASTDT = 1e-06 SIMDT = 1e-06 CONTROLDT = 0.1 PLOTDT = 0.01 MAXTIME = 0.6 TRANSIENT_TIME = 2 VARIABLE_DT_FLAG = 1 DEFAULT_VOL = 5.2357e-16 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 simobjdump text str simundump geometry /kinetics/geometry 0 5.236e-16 3 sphere "" white black 2 \ 14 0 simundump kpool /kinetics/Pi 0 0 0 0 0 0 0 0 3.1416e+05 0 /kinetics/geometry \ 56 black -2 6 0 simundump kreac /kinetics/GTP_hydrolysis[1] 0 19.5 0.22 "" white black -2 13 \ 0 simundump kreac /kinetics/GTP_hydrolysis[2] 0 40 3.4377e-10 "" white black 3 \ 6 0 simundump kreac /kinetics/Ras_activation 0 418 5.5 "" white black -6 6 0 simundump kreac /kinetics/GAP_dissociation 0 46.5 3.8197e-06 "" white black 3 \ -6 0 simundump kreac /kinetics/NF1_binding 0 3.8197e-06 6.36 "" white black -6 -6 \ 0 simundump kpool /kinetics/RasGTP 0 0 1 1 3.1416e+05 3.1416e+05 0 0 3.1416e+05 \ 0 /kinetics/geometry 24 black -6 -14 0 simundump kpool /kinetics/RasGTP-NF1 0 0 0 0 0 0 0 0 3.1416e+05 0 \ /kinetics/geometry 14 black -6 -1 0 simundump kpool /kinetics/RasGTP-NF1* 0 0 0 0 0 0 0 0 3.1416e+05 0 \ /kinetics/geometry 6 black -6 13 0 simundump kpool /kinetics/RasGDP-NF1_Pi 0 0 0 0 0 0 0 0 3.1416e+05 0 \ /kinetics/geometry 11 black 3 13 0 simundump kpool /kinetics/RasGDP_NF1 0 0 0 0 0 0 0 0 3.1416e+05 0 \ /kinetics/geometry 48 black 3 0 0 simundump kpool /kinetics/RasGDP 0 0 0 0 0 0 0 0 3.1416e+05 0 \ /kinetics/geometry 61 black 3 -14 0 simundump doqcsinfo /kinetics/doqcsinfo 0 \ /home/pragati/models/RasGTPase/25Feb2006/RasGTPase.g RasGTPase pathway \ "Sharat J. Vayttaden and Pragati Jain, NCBS" \ "Robert A. Phillips, Jackie L. Hunter, John F. Eccleston, and Martin R. Webb" \ "" "General Mammalian" "E.coli Expression system" Cytosol, Qualitative \ "Phillips RA et al Biochemistry. 2003 Apr 8;42(13):3956-65. (Peer-reviewed publication)" \ "Exact GENESIS implementation" "Approximates original data " 4 14 0 simundump kpool /kinetics/NF1 0 0 9.9994 9.9994 3.1414e+06 3.1414e+06 0 0 \ 3.1416e+05 0 /kinetics/geometry 54 black -2 -6 0 simundump xgraph /graphs/conc1 0 0 0.6 0 0.78639 0 simundump xgraph /graphs/conc2 0 0 0.6 0 1 0 simundump xplot /graphs/conc1/GAP.Ras.GTP*.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 6 0 0 1 simundump xplot /graphs/conc2/Ras.GTP.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 24 0 0 1 simundump xplot /graphs/conc2/Pi.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 56 0 0 1 simundump xgraph /moregraphs/conc3 0 0 0.6 0 0.00019729 0 simundump xgraph /moregraphs/conc4 0 0 0.6 0 0.00019729 0 simundump xcoredraw /edit/draw 0 -8 6 -16 16 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 \ "Ras GTPase Activation by GTPase Activating Proteins" \ "Phillips RA et al (2003)" \ "Biochemistry 42(13):3956-65 " \ "" \ "Volume of NIH/3T3 cells roughly approximated as half a picoliter" \ "and size is approximated as 10 uM radius based on " \ "personal communication by Rainer Heintzmann" \ "" addmsg /kinetics/GTP_hydrolysis[2] /kinetics/Pi REAC B A addmsg /kinetics/RasGDP-NF1_Pi /kinetics/GTP_hydrolysis[1] PRODUCT n addmsg /kinetics/RasGTP-NF1* /kinetics/GTP_hydrolysis[1] SUBSTRATE n addmsg /kinetics/RasGDP-NF1_Pi /kinetics/GTP_hydrolysis[2] SUBSTRATE n addmsg /kinetics/Pi /kinetics/GTP_hydrolysis[2] PRODUCT n addmsg /kinetics/RasGDP_NF1 /kinetics/GTP_hydrolysis[2] PRODUCT n addmsg /kinetics/RasGTP-NF1 /kinetics/Ras_activation SUBSTRATE n addmsg /kinetics/RasGTP-NF1* /kinetics/Ras_activation PRODUCT n addmsg /kinetics/RasGDP_NF1 /kinetics/GAP_dissociation SUBSTRATE n addmsg /kinetics/RasGDP /kinetics/GAP_dissociation PRODUCT n addmsg /kinetics/NF1 /kinetics/GAP_dissociation PRODUCT n addmsg /kinetics/RasGTP-NF1 /kinetics/NF1_binding PRODUCT n addmsg /kinetics/RasGTP /kinetics/NF1_binding SUBSTRATE n addmsg /kinetics/NF1 /kinetics/NF1_binding SUBSTRATE n addmsg /kinetics/NF1_binding /kinetics/RasGTP REAC A B addmsg /kinetics/NF1_binding /kinetics/RasGTP-NF1 REAC B A addmsg /kinetics/Ras_activation /kinetics/RasGTP-NF1 REAC A B addmsg /kinetics/Ras_activation /kinetics/RasGTP-NF1* REAC B A addmsg /kinetics/GTP_hydrolysis[1] /kinetics/RasGTP-NF1* REAC A B addmsg /kinetics/GTP_hydrolysis[1] /kinetics/RasGDP-NF1_Pi REAC B A addmsg /kinetics/GTP_hydrolysis[2] /kinetics/RasGDP-NF1_Pi REAC A B addmsg /kinetics/GTP_hydrolysis[2] /kinetics/RasGDP_NF1 REAC B A addmsg /kinetics/GAP_dissociation /kinetics/RasGDP_NF1 REAC A B addmsg /kinetics/GAP_dissociation /kinetics/RasGDP REAC B A addmsg /kinetics/GAP_dissociation /kinetics/NF1 REAC B A addmsg /kinetics/NF1_binding /kinetics/NF1 REAC A B addmsg /kinetics/RasGTP-NF1* /graphs/conc1/GAP.Ras.GTP*.Co PLOT Co *GAP.Ras.GTP*.Co *6 addmsg /kinetics/RasGTP /graphs/conc2/Ras.GTP.Co PLOT Co *Ras.GTP.Co *24 addmsg /kinetics/Pi /graphs/conc2/Pi.Co PLOT Co *Pi.Co *56 enddump // End of dump call /kinetics/Pi/notes LOAD \ "Inorganic Phosphate is released (Pi)" \ "" \ "" call /kinetics/GTP_hydrolysis[1]/notes LOAD \ "First step in hydrolysis of GTP bound to" \ "Ras complexed with NF1 - a mammalian GAP" \ "" \ "Kf = 19.5 /sec" \ "Kb = 0.22 /sec" \ "" \ "Table 3, Phillips RA et al 2003" \ "Biochemistry 42: 3956-3965" call /kinetics/GTP_hydrolysis[2]/notes LOAD \ "Second step in hydrolysis of GTP bound to" \ "Ras is complexed with NF1 - a mammalian GAP" \ "" \ "Kf = 40 /sec" \ "Kb = 108 /M/sec = 1.08e-04 /uM/sec" \ "" \ "Phillips RA et al 2003" \ "Biochemistry 42: 3956-3965" call /kinetics/Ras_activation/notes LOAD \ "Activation of Ras by GAP (i.e NF1)" \ "" \ "Kf = 418 /sec" \ "Kb = 5.5 /sec" \ "" \ "Table 3, Phillips RA et al 2003" \ "Biochemistry 42: 3956-3965" call /kinetics/GAP_dissociation/notes LOAD \ "Dissociation of NF1 from Ras.GDP" \ "NF1 is a mammalian GAP" \ "" \ "Kf = 46.5 /sec" \ "Kb = 1.2 /sec/uM" \ "" \ "Table 3, Phillips RA et al 2003" \ "Biochemistry 42: 3956-3965" call /kinetics/NF1_binding/notes LOAD \ "Binding of NF1 to Ras.GTP" \ "NF1 is a mammalian GAP" \ "" \ "Kd = 5.3 uM" \ "" \ "Table 3, Phillips RA et al 2003 " \ "Biochemistry 42: 3956-3965" call /kinetics/RasGTP/notes LOAD \ "The concentration of Ras GTP is 1 um." \ "Ref: Fig-2 " \ "Phillips RA et al " \ "Biochemistry 2003, 42, 3956-3965." \ "" call /kinetics/RasGTP-NF1/notes LOAD \ "NF1 bound to N-ras complexed to GTP" \ "NF1 is a mammalian GAP" \ "" \ "Phillips RA et al 2003 " \ "Biochemistry 42: 3956-3965" call /kinetics/RasGTP-NF1*/notes LOAD \ "NF1 bound to activated N-ras complexed to GTP" \ "NF1 is a mammalian GAP" \ "" \ "Phillips RA et al 2003" \ "Biochemistry 42: 3956-3965" call /kinetics/RasGDP-NF1_Pi/notes LOAD \ "NF1 bound to N-ras complexed to GDP.Pi" \ "NF1 is a GAP" \ "" \ "Phillips RA et al 2003" \ "Biochemistry 42: 3956-3965" call /kinetics/RasGDP_NF1/notes LOAD \ "NF1 bound to N-ras complexed to GDP" \ "NF1 is a mammalian GAP" \ "" \ "Phillips RA et al 2003" \ "Biochemistry 42: 3956-3965" call /kinetics/RasGDP/notes LOAD \ "Inactive Ras GDP is formed." call /kinetics/doqcsinfo/notes LOAD \ "Ras is an important regulator of cell growth in all eukaryotic cells. The model " \ "represent hydrolysis of active Ras-bound GTP to give inactive Ras-bound GDP catalyzed " \ "by GTPase activating proteins i.e NF1. The inactive Ras-bound GDP turns signalling " \ "protein off." call /kinetics/NF1/notes LOAD \ "Neurofibromin a mammalian GAP" \ "NF1 conc = 10 um pp.3959" \ "" \ "Refer: Phillips RA et al 2003" \ "Biochemistry 42: 3956-3965" \ "" complete_loading