//genesis // kkit Version 10 flat dumpfile // Saved on Mon Jan 19 16:45:11 2004 include kkit {argv 1} FASTDT = 1e-06 SIMDT = 0.0001 CONTROLDT = 0.1 PLOTDT = 0.01 MAXTIME = 0.8 TRANSIENT_TIME = 2 VARIABLE_DT_FLAG = 0 DEFAULT_VOL = 5.2357e-16 VERSION = 10.0 setfield /file/modpath value /home2/bhalla/scripts/modules kparms //genesis initdump -version 3 -ignoreorphans 1 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 kpool CoTotal CoInit Co n nInit nTotal nMin vol slave_enable notes \ 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 linkinfo xtree_fg_req xtree_textfg_req uplink downlink x y z simobjdump uplink xtree_fg_req xtree_textfg_req x y z simobjdump downlink xtree_fg_req xtree_textfg_req x y z simobjdump mirror notes xtree_fg_req x y z simundump kpool /kinetics/Pi 0 0 0 0 0 0 0 0 3.1416e+05 0 "" 56 black -6 -13 \ 0 simundump kreac /kinetics/GTP_hydrolysis[1] 0 19.5 0.22 "" white black 1 -13 \ 0 simundump kreac /kinetics/GTP_hydrolysis[2] 0 7.8 3.4377e-10 "" white black \ -2 -9 0 simundump kpool /kinetics/Ras.GTP 0 1 0.00019099 0.00019099 60 60 3.1416e+05 \ 0 3.1416e+05 0 "" 24 black 5 10 0 simundump kpool /kinetics/Ras.GDP 0 1 0.063471 0.063471 19940 19940 \ 3.1416e+05 0 3.1416e+05 0 "" 61 black -4 10 0 simundump kreac /kinetics/Ras_activation 0 418 5.5 "" white black 1 -3 0 simundump kreac /kinetics/GTP_exchange 0 0.00034 0.00042 "" white black 1 14 \ 0 simundump kreac /kinetics/GAP_binding 0 3.1831e-06 5.3 "" white black 1 8 0 simundump kreac /kinetics/GAP_dissociation 0 46.5 3.8197e-06 "" white black \ -2 0 0 simundump kpool /kinetics/GAP.Ras.GDP 0 0 0 0 0 0 0 0 3.1416e+05 0 "" 48 \ black -4 -4 0 simundump kpool /kinetics/GAP.Ras.GTP* 0 0 0 0 0 0 0 0 3.1416e+05 0 "" 6 \ black 5 -8 0 simundump kpool /kinetics/GAP.Ras.GDP.Pi 0 0 0 0 0 0 0 0 3.1416e+05 0 "" 11 \ black -3 -16 0 simundump kpool /kinetics/GAP 0 10 10 10 3.1416e+06 3.1416e+06 3.1416e+06 0 \ 3.1416e+05 0 "" 40 black 1 3 0 simundump kpool /kinetics/GAP.Ras.GTP 0 0 0 0 0 0 0 0 3.1416e+05 0 "" 14 \ black 5 5 0 simundump xgraph /graphs/conc1 0 0 0.8 0 0.07 0 simundump xgraph /graphs/conc2 0 0 0.8 0 0.00019729 0 simundump xplot /graphs/conc1/Ras.GDP.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 61 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/GAP.Ras.GTP.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 14 0 0 1 simundump xplot /graphs/conc2/GAP.Ras.GTP*.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 6 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 0.8 0 0.00019729 0 simundump xgraph /moregraphs/conc4 0 0 0.8 0 0.00019729 0 simundump xcoredraw /edit/draw 0 -8 7 -18 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" \ "Rates adapted from Robert A. Phillips 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/GAP.Ras.GDP.Pi /kinetics/GTP_hydrolysis[1] PRODUCT n addmsg /kinetics/GAP.Ras.GTP* /kinetics/GTP_hydrolysis[1] SUBSTRATE n addmsg /kinetics/GAP.Ras.GDP.Pi /kinetics/GTP_hydrolysis[2] SUBSTRATE n addmsg /kinetics/Pi /kinetics/GTP_hydrolysis[2] PRODUCT n addmsg /kinetics/GAP.Ras.GDP /kinetics/GTP_hydrolysis[2] PRODUCT n addmsg /kinetics/GAP_binding /kinetics/Ras.GTP REAC A B addmsg /kinetics/GTP_exchange /kinetics/Ras.GTP REAC B A addmsg /kinetics/GAP_dissociation /kinetics/Ras.GDP REAC B A addmsg /kinetics/GTP_exchange /kinetics/Ras.GDP REAC A B addmsg /kinetics/GAP.Ras.GTP /kinetics/Ras_activation SUBSTRATE n addmsg /kinetics/GAP.Ras.GTP* /kinetics/Ras_activation PRODUCT n addmsg /kinetics/Ras.GDP /kinetics/GTP_exchange SUBSTRATE n addmsg /kinetics/Ras.GTP /kinetics/GTP_exchange PRODUCT n addmsg /kinetics/GAP /kinetics/GAP_binding SUBSTRATE n addmsg /kinetics/GAP.Ras.GTP /kinetics/GAP_binding PRODUCT n addmsg /kinetics/Ras.GTP /kinetics/GAP_binding SUBSTRATE n addmsg /kinetics/GAP.Ras.GDP /kinetics/GAP_dissociation SUBSTRATE n addmsg /kinetics/GAP /kinetics/GAP_dissociation PRODUCT n addmsg /kinetics/Ras.GDP /kinetics/GAP_dissociation PRODUCT n addmsg /kinetics/GTP_hydrolysis[2] /kinetics/GAP.Ras.GDP REAC B A addmsg /kinetics/GAP_dissociation /kinetics/GAP.Ras.GDP REAC A B addmsg /kinetics/Ras_activation /kinetics/GAP.Ras.GTP* REAC B A addmsg /kinetics/GTP_hydrolysis[1] /kinetics/GAP.Ras.GTP* REAC A B addmsg /kinetics/GTP_hydrolysis[1] /kinetics/GAP.Ras.GDP.Pi REAC B A addmsg /kinetics/GTP_hydrolysis[2] /kinetics/GAP.Ras.GDP.Pi REAC A B addmsg /kinetics/GAP_binding /kinetics/GAP REAC A B addmsg /kinetics/GAP_dissociation /kinetics/GAP REAC B A addmsg /kinetics/GAP_binding /kinetics/GAP.Ras.GTP REAC B A addmsg /kinetics/Ras_activation /kinetics/GAP.Ras.GTP REAC A B addmsg /kinetics/Ras.GDP /graphs/conc1/Ras.GDP.Co PLOT Co *Ras.GDP.Co *61 addmsg /kinetics/Ras.GTP /graphs/conc2/Ras.GTP.Co PLOT Co *Ras.GTP.Co *24 addmsg /kinetics/GAP.Ras.GTP /graphs/conc2/GAP.Ras.GTP.Co PLOT Co *GAP.Ras.GTP.Co *14 addmsg /kinetics/GAP.Ras.GTP* /graphs/conc2/GAP.Ras.GTP*.Co PLOT Co *GAP.Ras.GTP*.Co *6 addmsg /kinetics/Pi /graphs/conc2/Pi.Co PLOT Co *Pi.Co *56 enddump // End of dump call /kinetics/Pi/notes LOAD \ "Pi" \ "" \ "Susan E. Neal et al 1988" \ "JBC 263(36):19718-19722" 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, Robert A. Phillips 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 = 7.8 /sec" \ "Kb = 108 /M/sec = 1.08e-04 /uM/sec" \ "" \ "Table 3, Robert A. Phillips et al 2003" \ "Biochemistry 42: 3956-3965" call /kinetics/Ras.GTP/notes LOAD \ "In NIH 3T3 cells <0.3% of Ras is in the " \ "active GTP-bound state. These cells contain " \ "approx. 20,000 Ras molecules per cell" \ "Therefore approx. 60 molecules of Ras.GTP " \ "are present in a normal NIH 3T3 cell" \ "" \ "Jurgen S. Scheele et al 1995" \ "PNAS USA 92:1097-1100" call /kinetics/Ras.GDP/notes LOAD \ "In NIH 3T3 cells <0.3% of Ras is in the " \ "active GTP-bound state. These cells contain " \ "approx. 20,000 Ras molecules per cell" \ "Therefore approx. 19940 molecules of Ras.GDP " \ "are present in a normal NIH 3T3 cell" \ "" \ "Jurgen S. Scheele et al 1995" \ "PNAS USA 92:1097-1100" call /kinetics/Ras_activation/notes LOAD \ "Activation of Ras by GAp (here NF1)" \ "" \ "Kf = 418 /sec" \ "Kb = 5.5 /sec" \ "" \ "Table 3, Robert A. Phillips et al 2003" \ "Biochemistry 42: 3956-3965" call /kinetics/GTP_exchange/notes LOAD \ "GDP bound to p21 N-Ras dissociates and almost immediately" \ "GTP associates with Ras protein" \ "" \ "Rate constants at 37 C" \ "kf = 3.4e-04 /sec" \ "kb = 4.2e-04 /sec" \ "" \ "Table I, Susan E. Neal et al 1988" \ "JBC 263(36):19718-19722" call /kinetics/GAP_binding/notes LOAD \ "Binding of NF1 to Ras.GTP" \ "NF1 is a mammalian GAP" \ "" \ "Kd = 5.3 uM" \ "" \ "Table 3, Robert A. Phillips 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, Robert A. Phillips et al 2003" \ "Biochemistry 42: 3956-3965" call /kinetics/GAP.Ras.GDP/notes LOAD \ "NF1 bound to N-ras complexed to GDP" \ "NF1 is a mammalian GAP" \ "" \ "Robert A. Phillips et al 2003" \ "Biochemistry 42: 3956-3965" call /kinetics/GAP.Ras.GTP*/notes LOAD \ "NF1 bound to activated N-ras complexed to GTP" \ "NF1 is a mammalian GAP" \ "" \ "Robert A. Phillips et al 2003" \ "Biochemistry 42: 3956-3965" call /kinetics/GAP.Ras.GDP.Pi/notes LOAD \ "NF1 bound to N-ras complexed to GDP.Pi" \ "NF1 is a GAP" \ "" \ "Robert A. Phillips et al 2003" \ "Biochemistry 42: 3956-3965" call /kinetics/GAP/notes LOAD \ "NF1: Neurofibromin a mammalian GAP" \ "" \ "NF1 conc. = 10uM pp.3959" \ "" \ "Robert A. Phillips et al 2003" \ "Biochemistry 42: 3956-3965" call /kinetics/GAP.Ras.GTP/notes LOAD \ "NF1 bound to N-ras complexed to GTP" \ "NF1 is a mammalian GAP" \ "" \ "Robert A. Phillips et al 2003" \ "Biochemistry 42: 3956-3965" complete_loading