//genesis // kkit Version 11 flat dumpfile // Saved on Thu Feb 12 16:50:41 2009 include kkit {argv 1} FASTDT = 2e-06 SIMDT = 0.001 CONTROLDT = 1 PLOTDT = 10 MAXTIME = 1000 TRANSIENT_TIME = 2 VARIABLE_DT_FLAG = 1 DEFAULT_VOL = 1e-15 VERSION = 11.0 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 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 simobjdump doqcsinfo filename accessname accesstype transcriber developer \ citation species tissue cellcompartment methodology sources \ model_implementation model_validation editfunc simundump geometry /kinetics/geometry 0 1e-15 3 sphere "" white black 0 0 0 simundump text /kinetics/notes 0 "" call /kinetics/notes LOAD \ "" simundump text /kinetics/geometry/notes 0 "" call /kinetics/geometry/notes LOAD \ "" simundump group /kinetics/CaM 1 blue black x 0 0 "" defaultfile defaultfile.g \ 0 fbb0ff81553508bc01f3dd51428742fb 0 21 42 0 simundump text /kinetics/CaM/notes 0 "" call /kinetics/CaM/notes LOAD \ "" simundump kpool /kinetics/CaM/CaM 1 -1e-12 20 20 1.2e+07 1.2e+07 0 0 6e+05 0 \ /kinetics/geometry pink blue 20 40 0 simundump text /kinetics/CaM/CaM/notes 0 \ "There is a LOT of this in the cell: upto 1% of total protein mass. (Alberts et al)\nSay 25 uM. Meyer et al Science 256 1199-1202 1992 refer to studies saying\nit is comparable to CaMK levels. \n" call /kinetics/CaM/CaM/notes LOAD \ "There is a LOT of this in the cell: upto 1% of total protein mass. (Alberts et al)" \ "Say 25 uM. Meyer et al Science 256 1199-1202 1992 refer to studies saying" \ "it is comparable to CaMK levels. " \ "" simundump kreac /kinetics/CaM/CaM-Ca3-bind-Ca 1 7.7501e-07 10 "" white blue \ 15 24 0 simundump text /kinetics/CaM/CaM-Ca3-bind-Ca/notes 0 \ "Use K3 = 21.5 uM here from Stemmer and Klee table 3.\nkb/kf =21.5 * 6e5 so kf = 7.75e-7, kb = 10" call /kinetics/CaM/CaM-Ca3-bind-Ca/notes LOAD \ "Use K3 = 21.5 uM here from Stemmer and Klee table 3." \ "kb/kf =21.5 * 6e5 so kf = 7.75e-7, kb = 10" simundump kpool /kinetics/CaM/CaM-Ca3 1 -1e-12 0 0 0 0 0 0 6e+05 0 \ /kinetics/geometry hotpink blue 34 28 0 simundump text /kinetics/CaM/CaM-Ca3/notes 0 "" call /kinetics/CaM/CaM-Ca3/notes LOAD \ "" simundump kreac /kinetics/CaM/CaM-bind-Ca 1 1.4141e-05 8.4853 "" white blue \ 20 37 0 simundump text /kinetics/CaM/CaM-bind-Ca/notes 0 \ "Lets use the fast rate consts here. Since the rates are so different, I am not\nsure whether the order is relevant. These correspond to the TR2C fragment.\nWe use the Martin et al rates here, plus the Drabicowski binding consts.\nAll are scaled by 3X to cell temp.\nkf = 2e-10 kb = 72\nStemmer & Klee: K1=.9, K2=1.1. Assume 1.0uM for both. kb/kf=3.6e11.\nIf kb=72, kf = 2e-10 (Exactly the same !)...." call /kinetics/CaM/CaM-bind-Ca/notes LOAD \ "Lets use the fast rate consts here. Since the rates are so different, I am not" \ "sure whether the order is relevant. These correspond to the TR2C fragment." \ "We use the Martin et al rates here, plus the Drabicowski binding consts." \ "All are scaled by 3X to cell temp." \ "kf = 2e-10 kb = 72" \ "Stemmer & Klee: K1=.9, K2=1.1. Assume 1.0uM for both. kb/kf=3.6e11." \ "If kb=72, kf = 2e-10 (Exactly the same !)" \ "" \ "19 May 2006. Splitting the old CaM-TR2-bind-Ca reaction into" \ "two steps, each binding 1 Ca. This improves numerical" \ "stability and is conceptually better too." \ "" \ "Overall rates are the same, so each kf and kb is the " \ "square root of the earlier ones. So" \ "kf = 1.125e-4, kb = 8.4853" \ "" simundump kpool /kinetics/CaM/CaM-Ca2 1 -1e-12 0 0 0 0 0 0 6e+05 0 \ /kinetics/geometry pink blue 33 42 0 simundump text /kinetics/CaM/CaM-Ca2/notes 0 \ "This is the intermediate where the TR2 end (the high-affinity end) has\nbound the Ca but the TR1 end has not." call /kinetics/CaM/CaM-Ca2/notes LOAD \ "This is the intermediate where the TR2 end (the high-affinity end) has" \ "bound the Ca but the TR1 end has not." simundump kreac /kinetics/CaM/CaM-Ca2-bind-Ca 1 6.0001e-06 10 "" white blue \ 26 37 0 simundump text /kinetics/CaM/CaM-Ca2-bind-Ca/notes 0 \ "K3 = 21.5, K4 = 2.8. Assuming that the K4 step happens first, we get\nkb/kf = 2.8 uM = 1.68e6 so kf =6e-6 assuming kb = 10\n" call /kinetics/CaM/CaM-Ca2-bind-Ca/notes LOAD \ "K3 = 21.5, K4 = 2.8. Assuming that the K4 step happens first, we get" \ "kb/kf = 2.8 uM = 1.68e6 so kf =6e-6 assuming kb = 10" \ "" simundump kreac /kinetics/CaM/CaM-Ca-bind-Ca 1 1.4141e-05 8.4853 "" white \ blue 32 37 0 simundump text /kinetics/CaM/CaM-Ca-bind-Ca/notes 0 \ "Lets use the fast rate consts here. Since the rates are so different, I am not\nsure whether the order is relevant. These correspond to the TR2C fragment.\nWe use the Martin et al rates here, plus the Drabicowski binding consts.\nAll are scaled by 3X to cell temp.\nkf = 2e-10 kb = 72\nStemmer & Klee: K1=.9, K2=1.1. Assume 1.0uM for both. kb/kf=3.6e11.\nIf kb=72, kf = 2e-10 (Exactly the same !)...." call /kinetics/CaM/CaM-Ca-bind-Ca/notes LOAD \ "Lets use the fast rate consts here. Since the rates are so different, I am not" \ "sure whether the order is relevant. These correspond to the TR2C fragment." \ "We use the Martin et al rates here, plus the Drabicowski binding consts." \ "All are scaled by 3X to cell temp." \ "kf = 2e-10 kb = 72" \ "Stemmer & Klee: K1=.9, K2=1.1. Assume 1.0uM for both. kb/kf=3.6e11." \ "If kb=72, kf = 2e-10 (Exactly the same !)" \ "" \ "19 May 2006. Splitting the old CaM-TR2-bind-Ca reaction into" \ "two steps, each binding 1 Ca. This improves numerical" \ "stability and is conceptually better too." \ "" \ "Overall rates are the same, so each kf and kb is the " \ "square root of the earlier ones. So" \ "kf = 1.125e-4, kb = 8.4853" \ "" simundump kpool /kinetics/CaM/CaM-Ca 1 -1e-12 0 0 0 0 0 0 6e+05 0 \ /kinetics/geometry pink blue 27 43 0 simundump text /kinetics/CaM/CaM-Ca/notes 0 \ "This is the intermediate where the TR2 end (the high-affinity end) has\nbound the Ca but the TR1 end has not." call /kinetics/CaM/CaM-Ca/notes LOAD \ "This is the intermediate where the TR2 end (the high-affinity end) has" \ "bound the Ca but the TR1 end has not." simundump kpool /kinetics/PP2A 0 0 0.15 0.15 90000 90000 0 0 6e+05 0 \ /kinetics/geometry 4 black 17 4 0 simundump text /kinetics/PP2A/notes 0 "Protein Phosphatase" call /kinetics/PP2A/notes LOAD \ "Protein Phosphatase" simundump kenz /kinetics/PP2A/eEF2thr-56_dephospho 0 0 0 0 0 6e+05 4.4506e-07 \ 1.88 0.47 0 0 "" red 4 "" 29 11 0 simundump text /kinetics/PP2A/eEF2thr-56_dephospho/notes 0 "" call /kinetics/PP2A/eEF2thr-56_dephospho/notes LOAD \ "" simundump kpool /kinetics/S6K_thr-252 0 0 0 0 0 0 0 0 6e+05 0 \ /kinetics/geometry 6 black 4 13 0 simundump text /kinetics/S6K_thr-252/notes 0 "" call /kinetics/S6K_thr-252/notes LOAD \ "" simundump kenz /kinetics/S6K_thr-252/camkIII_phospho 0 0 0 0 0 6e+05 \ 8.3333e-06 4 1 0 0 "" red 6 "" 4 14 0 simundump text /kinetics/S6K_thr-252/camkIII_phospho/notes 0 "" call /kinetics/S6K_thr-252/camkIII_phospho/notes LOAD \ "" simundump kpool /kinetics/CaM-Ca4 1 0 0 0 0 0 0 0 6e+05 0 /kinetics/geometry \ blue yellow 17 38 0 simundump text /kinetics/CaM-Ca4/notes 0 "" call /kinetics/CaM-Ca4/notes LOAD \ "" simundump kpool /kinetics/CaMKIII 0 0 0.06 0.06 36000 36000 0 0 6e+05 0 \ /kinetics/geometry 32 black 3 24 0 simundump text /kinetics/CaMKIII/notes 0 "" call /kinetics/CaMKIII/notes LOAD \ "" simundump kpool /kinetics/CaMKIII_CaM-Ca4 0 0 0 0 0 0 0 0 6e+05 0 \ /kinetics/geometry 58 black 25 32 0 simundump text /kinetics/CaMKIII_CaM-Ca4/notes 0 "" call /kinetics/CaMKIII_CaM-Ca4/notes LOAD \ "" simundump kenz /kinetics/CaMKIII_CaM-Ca4/phospho 0 0 0 0 0 6e+05 4.1667e-05 \ 40 10 0 0 "" red 58 "" 21 30 0 simundump text /kinetics/CaMKIII_CaM-Ca4/phospho/notes 0 "" call /kinetics/CaMKIII_CaM-Ca4/phospho/notes LOAD \ "" simundump kpool /kinetics/eEF2 0 0 0.5 0.5 3e+05 3e+05 0 0 6e+05 0 \ /kinetics/geometry 27 black 39 29 0 simundump text /kinetics/eEF2/notes 0 "" call /kinetics/eEF2/notes LOAD \ "" simundump kpool /kinetics/eEFthr-56 0 0 0 0 0 0 0 0 6e+05 0 \ /kinetics/geometry white black 22 21 0 simundump text /kinetics/eEFthr-56/notes 0 "" call /kinetics/eEFthr-56/notes LOAD \ "" simundump kpool /kinetics/Ca 1 0 0.08 0.08 48000 48000 0 0 6e+05 0 \ /kinetics/geometry red black 8 35 0 simundump text /kinetics/Ca/notes 0 "" call /kinetics/Ca/notes LOAD \ "" simundump kpool /kinetics/Ca_input 0 0 0 0 0 0 0 0 6e+05 2 /kinetics/geometry \ 61 black 5 44 0 simundump text /kinetics/Ca_input/notes 0 "" call /kinetics/Ca_input/notes LOAD \ "" simundump kpool /kinetics/CaMKIII_basal 0 0 1e-05 1e-05 6 6 0 0 6e+05 0 \ /kinetics/geometry 45 black 16 0 0 simundump text /kinetics/CaMKIII_basal/notes 0 "" call /kinetics/CaMKIII_basal/notes LOAD \ "" simundump kenz /kinetics/CaMKIII_basal/eEF2thr56_basal 0 0 0 0 0 6e+05 \ 4.1667e-05 40 10 0 0 "" red 45 "" 20 8 0 simundump text /kinetics/CaMKIII_basal/eEF2thr56_basal/notes 0 "" call /kinetics/CaMKIII_basal/eEF2thr56_basal/notes LOAD \ "" simundump kpool /kinetics/CaMKIII* 0 0 0 0 0 0 0 0 6e+05 0 /kinetics/geometry \ 57 black 5 1 0 simundump text /kinetics/CaMKIII*/notes 0 "" call /kinetics/CaMKIII*/notes LOAD \ "" simundump kpool /kinetics/S6K_basal 0 0 0.001 0.001 600 600 0 0 6e+05 0 \ /kinetics/geometry 45 black 37 32 0 simundump text /kinetics/S6K_basal/notes 0 "" call /kinetics/S6K_basal/notes LOAD \ "" simundump kenz /kinetics/S6K_basal/CaMKIII_basal 0 0 0 0 0 6e+05 8.3342e-05 \ 40 10 0 0 "" red 45 "" 17 16 0 simundump text /kinetics/S6K_basal/CaMKIII_basal/notes 0 "" call /kinetics/S6K_basal/CaMKIII_basal/notes LOAD \ "" simundump kpool /kinetics/Translation_clx 0 0 0 0 0 0 0 0 6e+05 0 \ /kinetics/geometry 52 black 30 11 0 simundump text /kinetics/Translation_clx/notes 0 "" call /kinetics/Translation_clx/notes LOAD \ "" simundump kpool /kinetics/Ca_ext 0 0 0 0 0 0 0 0 6e+05 1 /kinetics/geometry \ blue black 16 42 0 simundump text /kinetics/Ca_ext/notes 0 "" call /kinetics/Ca_ext/notes LOAD \ "" simundump kpool /kinetics/Ca_sum 0 0 0 0 0 0 0 0 6e+05 0 /kinetics/geometry \ 47 black 10 38 0 simundump text /kinetics/Ca_sum/notes 0 "" call /kinetics/Ca_sum/notes LOAD \ "" simundump kreac /kinetics/Ca_diff 0 300 300 "" white black 3 36 0 simundump text /kinetics/Ca_diff/notes 0 "" call /kinetics/Ca_diff/notes LOAD \ "" simundump kreac /kinetics/dephosp_CaMKIII 0 0.07 0 "" white black 10 10 0 simundump text /kinetics/dephosp_CaMKIII/notes 0 "" call /kinetics/dephosp_CaMKIII/notes LOAD \ "" simundump kreac /kinetics/CaMKIII_bind_CaM-Ca4 0 0.000165 0.09 "" white black \ 4 28 0 simundump text /kinetics/CaMKIII_bind_CaM-Ca4/notes 0 "" call /kinetics/CaMKIII_bind_CaM-Ca4/notes LOAD \ "" simundump doqcsinfo /kinetics/doqcsinfo 0 CaMKIII.g CaMKIII Network \ "Pragati Jain, NCBS" "Pragati Jain, NCBS" "citation here" \ "General Mammalian" Brain "Surface, Cytosol, Nucleus" \ "Quantitative match to experiments, Qualitative" \ "Jain P, and Bhalla, U.S. PLoS Comput Biol. 2009 Feb;5(2). ( Peer-reviewed publication )" \ "Exact GENESIS implementation, Approximate implementation" \ "Approximates original data " show_dumpdb simundump text /kinetics/doqcsinfo/notes 0 \ "CaMKIII is activated by Ca2+ and inactivated by S6K. Since CaMKIII inhibits eEF2, \nthe net effect of Ca2+ on elongation is inhibitory and of S6K is excitatory\n" call /kinetics/doqcsinfo/notes LOAD \ "CaMKIII is activated by Ca2+ and inactivated by S6K. Since CaMKIII inhibits eEF2, " \ "the net effect of Ca2+ on elongation is inhibitory and of S6K is excitatory" \ "" simundump xgraph /graphs/conc1 0 0 1000 0 1 0 simundump xgraph /graphs/conc2 0 0 1000 0 1 0 simundump xplot /graphs/conc1/CaMKIII*.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 57 0 0 1 simundump xplot /graphs/conc2/eEFthr-56.Co 3 524288 \ "delete_plot.w ; edit_plot.D " white 0 0 1 simundump xplot /graphs/conc2/eEF2.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 27 0 0 1 simundump xgraph /moregraphs/conc3 0 0 100 0 1 0 simundump xgraph /moregraphs/conc4 0 0 100 0 1 0 simundump xcoredraw /edit/draw 0 -2 41 -2 46 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 \ "" \ " " addmsg /kinetics/CaM/CaM-bind-Ca /kinetics/CaM/CaM REAC A B addmsg /kinetics/CaM/CaM-Ca3 /kinetics/CaM/CaM-Ca3-bind-Ca SUBSTRATE n addmsg /kinetics/Ca /kinetics/CaM/CaM-Ca3-bind-Ca SUBSTRATE n addmsg /kinetics/CaM-Ca4 /kinetics/CaM/CaM-Ca3-bind-Ca PRODUCT n addmsg /kinetics/CaM/CaM-Ca2-bind-Ca /kinetics/CaM/CaM-Ca3 REAC B A addmsg /kinetics/CaM/CaM-Ca3-bind-Ca /kinetics/CaM/CaM-Ca3 REAC A B addmsg /kinetics/CaM/CaM /kinetics/CaM/CaM-bind-Ca SUBSTRATE n addmsg /kinetics/Ca /kinetics/CaM/CaM-bind-Ca SUBSTRATE n addmsg /kinetics/CaM/CaM-Ca /kinetics/CaM/CaM-bind-Ca PRODUCT n addmsg /kinetics/CaM/CaM-Ca2-bind-Ca /kinetics/CaM/CaM-Ca2 REAC A B addmsg /kinetics/CaM/CaM-Ca-bind-Ca /kinetics/CaM/CaM-Ca2 REAC B A addmsg /kinetics/CaM/CaM-Ca2 /kinetics/CaM/CaM-Ca2-bind-Ca SUBSTRATE n addmsg /kinetics/Ca /kinetics/CaM/CaM-Ca2-bind-Ca SUBSTRATE n addmsg /kinetics/CaM/CaM-Ca3 /kinetics/CaM/CaM-Ca2-bind-Ca PRODUCT n addmsg /kinetics/CaM/CaM-Ca /kinetics/CaM/CaM-Ca-bind-Ca SUBSTRATE n addmsg /kinetics/Ca /kinetics/CaM/CaM-Ca-bind-Ca SUBSTRATE n addmsg /kinetics/CaM/CaM-Ca2 /kinetics/CaM/CaM-Ca-bind-Ca PRODUCT n addmsg /kinetics/CaM/CaM-bind-Ca /kinetics/CaM/CaM-Ca REAC B A addmsg /kinetics/CaM/CaM-Ca-bind-Ca /kinetics/CaM/CaM-Ca REAC A B addmsg /kinetics/PP2A/eEF2thr-56_dephospho /kinetics/PP2A REAC eA B addmsg /kinetics/PP2A /kinetics/PP2A/eEF2thr-56_dephospho ENZYME n addmsg /kinetics/eEFthr-56 /kinetics/PP2A/eEF2thr-56_dephospho SUBSTRATE n addmsg /kinetics/S6K_thr-252/camkIII_phospho /kinetics/S6K_thr-252 REAC eA B addmsg /kinetics/S6K_thr-252 /kinetics/S6K_thr-252/camkIII_phospho ENZYME n addmsg /kinetics/CaMKIII /kinetics/S6K_thr-252/camkIII_phospho SUBSTRATE n addmsg /kinetics/CaMKIII_bind_CaM-Ca4 /kinetics/CaM-Ca4 REAC A B addmsg /kinetics/CaM/CaM-Ca3-bind-Ca /kinetics/CaM-Ca4 REAC B A addmsg /kinetics/CaMKIII_bind_CaM-Ca4 /kinetics/CaMKIII REAC A B addmsg /kinetics/S6K_thr-252/camkIII_phospho /kinetics/CaMKIII REAC sA B addmsg /kinetics/dephosp_CaMKIII /kinetics/CaMKIII REAC B A addmsg /kinetics/S6K_basal/CaMKIII_basal /kinetics/CaMKIII REAC sA B addmsg /kinetics/CaMKIII_bind_CaM-Ca4 /kinetics/CaMKIII_CaM-Ca4 REAC B A addmsg /kinetics/CaMKIII_CaM-Ca4/phospho /kinetics/CaMKIII_CaM-Ca4 REAC eA B addmsg /kinetics/CaMKIII_CaM-Ca4 /kinetics/CaMKIII_CaM-Ca4/phospho ENZYME n addmsg /kinetics/eEF2 /kinetics/CaMKIII_CaM-Ca4/phospho SUBSTRATE n addmsg /kinetics/CaMKIII_CaM-Ca4/phospho /kinetics/eEF2 REAC sA B addmsg /kinetics/CaMKIII_basal/eEF2thr56_basal /kinetics/eEF2 REAC sA B addmsg /kinetics/PP2A/eEF2thr-56_dephospho /kinetics/eEF2 MM_PRD pA addmsg /kinetics/CaMKIII_CaM-Ca4/phospho /kinetics/eEFthr-56 MM_PRD pA addmsg /kinetics/CaMKIII_basal/eEF2thr56_basal /kinetics/eEFthr-56 MM_PRD pA addmsg /kinetics/PP2A/eEF2thr-56_dephospho /kinetics/eEFthr-56 REAC sA B addmsg /kinetics/CaM/CaM-bind-Ca /kinetics/Ca REAC A B addmsg /kinetics/CaM/CaM-Ca2-bind-Ca /kinetics/Ca REAC A B addmsg /kinetics/CaM/CaM-Ca3-bind-Ca /kinetics/Ca REAC A B addmsg /kinetics/Ca_diff /kinetics/Ca REAC B A addmsg /kinetics/CaM/CaM-Ca-bind-Ca /kinetics/Ca REAC A B addmsg /kinetics/CaMKIII_basal/eEF2thr56_basal /kinetics/CaMKIII_basal REAC eA B addmsg /kinetics/CaMKIII_basal /kinetics/CaMKIII_basal/eEF2thr56_basal ENZYME n addmsg /kinetics/eEF2 /kinetics/CaMKIII_basal/eEF2thr56_basal SUBSTRATE n addmsg /kinetics/S6K_thr-252/camkIII_phospho /kinetics/CaMKIII* MM_PRD pA addmsg /kinetics/dephosp_CaMKIII /kinetics/CaMKIII* REAC A B addmsg /kinetics/S6K_basal/CaMKIII_basal /kinetics/CaMKIII* MM_PRD pA addmsg /kinetics/S6K_basal/CaMKIII_basal /kinetics/S6K_basal REAC eA B addmsg /kinetics/S6K_basal /kinetics/S6K_basal/CaMKIII_basal ENZYME n addmsg /kinetics/CaMKIII /kinetics/S6K_basal/CaMKIII_basal SUBSTRATE n addmsg /kinetics/Ca_input /kinetics/Ca_sum SUMTOTAL n nInit addmsg /kinetics/Ca_ext /kinetics/Ca_sum SUMTOTAL n nInit addmsg /kinetics/Ca_diff /kinetics/Ca_sum REAC A B addmsg /kinetics/Ca /kinetics/Ca_diff PRODUCT n addmsg /kinetics/Ca_sum /kinetics/Ca_diff SUBSTRATE n addmsg /kinetics/CaMKIII* /kinetics/dephosp_CaMKIII SUBSTRATE n addmsg /kinetics/CaMKIII /kinetics/dephosp_CaMKIII PRODUCT n addmsg /kinetics/CaM-Ca4 /kinetics/CaMKIII_bind_CaM-Ca4 SUBSTRATE n addmsg /kinetics/CaMKIII /kinetics/CaMKIII_bind_CaM-Ca4 SUBSTRATE n addmsg /kinetics/CaMKIII_CaM-Ca4 /kinetics/CaMKIII_bind_CaM-Ca4 PRODUCT n addmsg /kinetics/CaMKIII* /graphs/conc1/CaMKIII*.Co PLOT Co *CaMKIII*.Co *57 addmsg /kinetics/eEFthr-56 /graphs/conc2/eEFthr-56.Co PLOT Co *eEFthr-56.Co *white addmsg /kinetics/eEF2 /graphs/conc2/eEF2.Co PLOT Co *eEF2.Co *27 enddump // End of dump call /kinetics/CaM/CaM/notes LOAD \ "There is a LOT of this in the cell: upto 1% of total protein mass. (Alberts et al)" \ "Say 25 uM. Meyer et al Science 256 1199-1202 1992 refer to studies saying" \ "it is comparable to CaMK levels. " \ "" call /kinetics/CaM/CaM-Ca3-bind-Ca/notes LOAD \ "Use K3 = 21.5 uM here from Stemmer and Klee table 3." \ "kb/kf =21.5 * 6e5 so kf = 7.75e-7, kb = 10" call /kinetics/CaM/CaM-bind-Ca/notes LOAD \ "Lets use the fast rate consts here. Since the rates are so different, I am not" \ "sure whether the order is relevant. These correspond to the TR2C fragment." \ "We use the Martin et al rates here, plus the Drabicowski binding consts." \ "All are scaled by 3X to cell temp." \ "kf = 2e-10 kb = 72" \ "Stemmer & Klee: K1=.9, K2=1.1. Assume 1.0uM for both. kb/kf=3.6e11." \ "If kb=72, kf = 2e-10 (Exactly the same !)" \ "" \ "19 May 2006. Splitting the old CaM-TR2-bind-Ca reaction into" \ "two steps, each binding 1 Ca. This improves numerical" \ "stability and is conceptually better too." \ "" \ "Overall rates are the same, so each kf and kb is the " \ "square root of the earlier ones. So" \ "kf = 1.125e-4, kb = 8.4853" \ "" call /kinetics/CaM/CaM-Ca2/notes LOAD \ "This is the intermediate where the TR2 end (the high-affinity end) has" \ "bound the Ca but the TR1 end has not." call /kinetics/CaM/CaM-Ca2-bind-Ca/notes LOAD \ "K3 = 21.5, K4 = 2.8. Assuming that the K4 step happens first, we get" \ "kb/kf = 2.8 uM = 1.68e6 so kf =6e-6 assuming kb = 10" \ "" call /kinetics/CaM/CaM-Ca-bind-Ca/notes LOAD \ "Lets use the fast rate consts here. Since the rates are so different, I am not" \ "sure whether the order is relevant. These correspond to the TR2C fragment." \ "We use the Martin et al rates here, plus the Drabicowski binding consts." \ "All are scaled by 3X to cell temp." \ "kf = 2e-10 kb = 72" \ "Stemmer & Klee: K1=.9, K2=1.1. Assume 1.0uM for both. kb/kf=3.6e11." \ "If kb=72, kf = 2e-10 (Exactly the same !)" \ "" \ "19 May 2006. Splitting the old CaM-TR2-bind-Ca reaction into" \ "two steps, each binding 1 Ca. This improves numerical" \ "stability and is conceptually better too." \ "" \ "Overall rates are the same, so each kf and kb is the " \ "square root of the earlier ones. So" \ "kf = 1.125e-4, kb = 8.4853" \ "" call /kinetics/CaM/CaM-Ca/notes LOAD \ "This is the intermediate where the TR2 end (the high-affinity end) has" \ "bound the Ca but the TR1 end has not." call /kinetics/PP2A/notes LOAD \ "Protein Phosphatase" call /kinetics/doqcsinfo/notes LOAD \ "CaMKIII is activated by Ca2+ and inactivated by S6K. Since CaMKIII inhibits eEF2, " \ "the net effect of Ca2+ on elongation is inhibitory and of S6K is excitatory" \ "" complete_loading