//genesis // kkit Version 11 flat dumpfile // Saved on Thu Jul 21 16:18:10 2005 include kkit {argv 1} FASTDT = 0.0001 SIMDT = 0.001 CONTROLDT = 10 PLOTDT = 10 MAXTIME = 2000 TRANSIENT_TIME = 10 VARIABLE_DT_FLAG = 1 DEFAULT_VOL = 9e-20 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 x y z simobjdump kpool DiffConst CoInit Co n nInit mwt nMin vol slave_enable \ comptname 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 doqcsinfo filename accessname accesstype transcriber developer \ citation species tissue cellcompartment methodology sources \ model_implementation model_validation editfunc simundump geometry /kinetics/geometry 0 9e-20 3 sphere "" -211 143 0 simundump geometry /kinetics/geometry[1] 0 1e-20 3 sphere 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blue blue x 0 0 "" defaultfile defaultfile.g 0 \ 8d0e973f34b6d4ab7f8d392323b51ca6 0 -224.53 103.53 0 simundump kpool /kinetics/AC/ATP 1 0 2000 2000 1.08e+05 1.08e+05 0 0 54 4 \ /kinetics/geometry red blue -225.04 102.13 0 simundump kpool /kinetics/AC/AC1-CaM 1 0 0 0 0 0 0 0 54 0 /kinetics/geometry \ orange blue -227.48 103.74 0 simundump kenz /kinetics/AC/AC1-CaM/kenz 1 0 0 0 0 54 0.0013889 18 4.5 0 1 "" \ red orange "" -227.52 102.61 0 simundump kpool /kinetics/AC/AC1 1 0 0.074074 0.074074 4 4 0 0 54 0 \ /kinetics/geometry orange blue -231.25 105.61 0 simundump kreac /kinetics/AC/CaM-bind-AC1 1 0.92592 1 "" white blue -229 106 \ 0 simundump kpool /kinetics/AC/AC2* 1 0 0 0 0 0 0 0 54 0 /kinetics/geometry \ yellow blue -225.65 98.48 0 simundump kenz /kinetics/AC/AC2*/kenz 1 0 0 0 0 54 0.00061728 8 2 0 1 "" red \ yellow "" -225.77 99.337 0 simundump kpool /kinetics/AC/AC2 1 0 0.074074 0.074074 4 4 0 0 54 0 \ /kinetics/geometry yellow blue -224.61 96.697 0 simundump kreac 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/kinetics/PKA/PKA-inhibitor 1 0 0.25926 0.25926 14 14 0 0 54 \ 0 /kinetics/geometry cyan blue -254.77 81.379 0 simundump kreac /kinetics/PKA/inhib-PKA 1 1.1111 1 "" white blue -251.98 \ 82.003 0 simundump kpool /kinetics/PKA/inhibited-PKA 1 0 0 0 0 0 0 0 54 0 \ /kinetics/geometry cyan blue -255.4 82.978 0 simundump kpool /kinetics/PKC-active 1 0 0.1 0.1 5.4 5.4 0 0 54 0 \ /kinetics/geometry red black -207 130 0 simundump kenz /kinetics/PKC-active/phosph-AC2 1 4.007e-05 4.007e-05 \ 0.0021638 0.0021638 54 0.011111 16 4 0 0 "" red red "" -213.68 109.73 0 simundump kpool /kinetics/CaMKII-thr305-PSD 0 0 0 0 0 0 0 0 6 0 \ /kinetics/geometry[1] 30 black -242 168 0 simundump doqcsinfo /kinetics/doqcsinfo 0 model3_db.g CaMKII_model3 network \ "Upinder S. Bhalla, NCBS" "Arnold Hayer and Upinder S. Bhalla, NCBS" \ "Hayer and Bhalla, PLoS Comput Biol, 2005." "General Mammalian" Neuronal \ "Synaptic Spine, Postsynaptic Density" \ "Quantitative match to experiments, Qualitative" \ "Hayer A, Bhalla US PLoS Comput Biol. 2005 Jul;1(2):137-54. Epub 2005 Jul 29. ( Peer-reviewed publication )" "Exact GENESIS implementation" \ "Replicates original data , Approximates original data " show_dumpdb simundump xgraph /graphs/conc1 0 0 2000 0 1 0 simundump xgraph /graphs/conc2 0 0 2000 0 1 0 simundump xplot /graphs/conc1/actCaMKII-PSD.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 12 0 0 1 simundump xplot /graphs/conc1/tot_CaMKII_PSD.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 23 0 0 1 simundump xplot /graphs/conc1/act_CaMKII_cyt.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 14 0 0 1 simundump xplot /graphs/conc1/tot_CaMKII_cyt.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 24 0 0 1 simundump xplot /graphs/conc1/CaM_Ca_n-CaNAB.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 1 0 0 1 simundump xplot /graphs/conc2/CaM-Ca4-PSD.Co 3 524288 \ "delete_plot.w ; edit_plot.D " blue 0 0 1 simundump xgraph /moregraphs/conc3 0 0 100 0 1 0 simundump xgraph /moregraphs/conc4 0 0 100 0 1 0 simundump xplot /moregraphs/conc3/PP1-active_PSD.Co 3 524288 \ "delete_plot.w ; edit_plot.D " cyan 0 0 1 simundump xplot /moregraphs/conc3/PKA-active.Co 3 524288 \ "delete_plot.w ; edit_plot.D " yellow 0 0 1 simundump xplot /moregraphs/conc3/Ca.Co 3 524288 \ "delete_plot.w ; edit_plot.D " red 0 0 1 simundump xplot /moregraphs/conc4/PP1-active.Co 3 524288 \ "delete_plot.w ; edit_plot.D " cyan 0 0 1 simundump xplot /moregraphs/conc4/CaM-Ca4.Co 3 524288 \ "delete_plot.w ; edit_plot.D " blue 0 0 1 simundump xcoredraw /edit/draw 0 -345 2 -2 189 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 \ "Merge of PKA and AC from transloc_feb05k.g" \ "Merge the whole lot into CaMKII_bis_onlyk.g" \ "to get CaMKII_bis_fullPKA.g" \ "" \ "21 June 2005. Naming fix: thr306 to 305 for consistency. Saved as" \ "CaMKII_PKA_traff.g" \ "" addmsg /kinetics/CaMKII/CaMKII-bind-CaM /kinetics/CaM-Ca4 REAC A B addmsg /kinetics/CaMKII/CaMK-thr286-bind-CaM /kinetics/CaM-Ca4 REAC A B addmsg /kinetics/CaM-Ca3-bind-Ca /kinetics/CaM-Ca4 REAC B A addmsg /kinetics/PP2B/CaMCa4-bind-CaNAB /kinetics/CaM-Ca4 REAC A B addmsg /kinetics/equilib /kinetics/CaM-Ca4 REAC B A addmsg /kinetics/AC/CaM-bind-AC1 /kinetics/CaM-Ca4 REAC A B addmsg /kinetics/AC/CaM_bind_PDE1 /kinetics/CaM-Ca4 REAC A B addmsg /kinetics/PP1/Inact-PP1 /kinetics/PP1-active REAC A B addmsg /kinetics/PP1/dissoc-PP1-I1 /kinetics/PP1-active REAC B A addmsg /kinetics/PP1-active/Deph-thr286 /kinetics/PP1-active REAC eA B addmsg /kinetics/PP1-active/Deph-thr286b /kinetics/PP1-active REAC eA B addmsg /kinetics/PP1-active/Deph-thr305 /kinetics/PP1-active REAC eA B addmsg /kinetics/PP1-active/Deph-thr286c /kinetics/PP1-active REAC eA B addmsg /kinetics/PP1-active/Deph-thr305a /kinetics/PP1-active REAC eA B addmsg /kinetics/PP1-active /kinetics/PP1-active/Deph-thr286 ENZYME n addmsg /kinetics/CaMKII/CaMKII-thr286*-CaM /kinetics/PP1-active/Deph-thr286 SUBSTRATE n addmsg /kinetics/PP1-active /kinetics/PP1-active/Deph-thr286b ENZYME n addmsg /kinetics/CaMKII/CaMKII-thr286 /kinetics/PP1-active/Deph-thr286b SUBSTRATE n addmsg /kinetics/PP1-active /kinetics/PP1-active/Deph-thr305 ENZYME n addmsg /kinetics/CaMKII/CaMKII*** /kinetics/PP1-active/Deph-thr305 SUBSTRATE n addmsg /kinetics/PP1-active /kinetics/PP1-active/Deph-thr286c ENZYME n addmsg /kinetics/CaMKII/CaMKII*** /kinetics/PP1-active/Deph-thr286c SUBSTRATE n addmsg /kinetics/PP1-active /kinetics/PP1-active/Deph-thr305a ENZYME n addmsg /kinetics/CaMKII/CaMK-thr305 /kinetics/PP1-active/Deph-thr305a SUBSTRATE n addmsg /kinetics/CaM/CaM-TR2-bind-Ca /kinetics/Ca REAC A B addmsg /kinetics/CaM/CaM-TR2-bind-Ca /kinetics/Ca REAC A B addmsg /kinetics/CaM/CaM-TR2-Ca2-bind-Ca /kinetics/Ca REAC A B addmsg /kinetics/CaM-Ca3-bind-Ca /kinetics/Ca REAC A B addmsg /kinetics/PP2B/Ca-bind-CaNAB-Ca2 /kinetics/Ca REAC A B addmsg /kinetics/PP2B/Ca-bind-CaNAB-Ca2 /kinetics/Ca REAC A B addmsg /kinetics/PP2B/Ca-bind-CaNAB /kinetics/Ca REAC A B addmsg /kinetics/PP2B/Ca-bind-CaNAB /kinetics/Ca REAC A B addmsg /kinetics/Ca_stoch_cyt /kinetics/Ca REAC B A addmsg /kinetics/PKA-active/PKA-phosph-I1 /kinetics/PKA-active REAC eA B addmsg /kinetics/PKA-active/PKA-phosph-I1_PSD /kinetics/PKA-active REAC eA B addmsg /kinetics/PKA-active/phosph-PDE /kinetics/PKA-active REAC eA B addmsg /kinetics/PKA/Release-C1 /kinetics/PKA-active REAC B A addmsg /kinetics/PKA/Release-C2 /kinetics/PKA-active REAC B A addmsg /kinetics/PKA/inhib-PKA /kinetics/PKA-active REAC A B addmsg /kinetics/PKA-active /kinetics/PKA-active/PKA-phosph-I1 ENZYME n addmsg /kinetics/PP1/I1 /kinetics/PKA-active/PKA-phosph-I1 SUBSTRATE n addmsg /kinetics/PKA-active /kinetics/PKA-active/PKA-phosph-I1_PSD ENZYME n addmsg /kinetics/PP1_PSD/I1 /kinetics/PKA-active/PKA-phosph-I1_PSD SUBSTRATE n addmsg /kinetics/PKA-active /kinetics/PKA-active/phosph-PDE ENZYME n addmsg /kinetics/AC/cAMP-PDE /kinetics/PKA-active/phosph-PDE SUBSTRATE n addmsg /kinetics/CaMKII/CaMKII-bind-CaM /kinetics/CaMKII/CaMKII REAC A B addmsg /kinetics/back_1 /kinetics/CaMKII/CaMKII REAC B A addmsg /kinetics/PP1-active/Deph-thr286b /kinetics/CaMKII/CaMKII MM_PRD pA addmsg /kinetics/PP1-active/Deph-thr305a /kinetics/CaMKII/CaMKII MM_PRD pA addmsg /kinetics/CaMKII/CaMKII-bind-CaM /kinetics/CaMKII/CaMKII-CaM REAC B A addmsg /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_286 /kinetics/CaMKII/CaMKII-CaM REAC sA B addmsg /kinetics/CaMKII/tot_autonomous_CaMKII/auton_286 /kinetics/CaMKII/CaMKII-CaM REAC sA B addmsg /kinetics/transloc_1 /kinetics/CaMKII/CaMKII-CaM REAC A B addmsg /kinetics/PP1-active/Deph-thr286 /kinetics/CaMKII/CaMKII-CaM MM_PRD pA addmsg /kinetics/CaMKII/CaMK-thr286-bind-CaM /kinetics/CaMKII/CaMKII-thr286*-CaM REAC B A addmsg /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_286 /kinetics/CaMKII/CaMKII-thr286*-CaM MM_PRD pA addmsg /kinetics/CaMKII/tot_autonomous_CaMKII/auton_286 /kinetics/CaMKII/CaMKII-thr286*-CaM MM_PRD pA addmsg /kinetics/transloc_2 /kinetics/CaMKII/CaMKII-thr286*-CaM REAC A B addmsg /kinetics/PP1-active/Deph-thr286 /kinetics/CaMKII/CaMKII-thr286*-CaM REAC sA B addmsg /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_305 /kinetics/CaMKII/CaMKII*** MM_PRD pA addmsg /kinetics/CaMKII/tot_autonomous_CaMKII/auton_305 /kinetics/CaMKII/CaMKII*** MM_PRD pA addmsg /kinetics/PP1-active/Deph-thr305 /kinetics/CaMKII/CaMKII*** REAC sA B addmsg /kinetics/PP1-active/Deph-thr286c /kinetics/CaMKII/CaMKII*** REAC sA B addmsg /kinetics/CaM-Ca4 /kinetics/CaMKII/CaMKII-bind-CaM SUBSTRATE n addmsg /kinetics/CaMKII/CaMKII /kinetics/CaMKII/CaMKII-bind-CaM SUBSTRATE n addmsg /kinetics/CaMKII/CaMKII-CaM /kinetics/CaMKII/CaMKII-bind-CaM PRODUCT n addmsg /kinetics/CaMKII/CaMKII-thr286 /kinetics/CaMKII/CaMK-thr286-bind-CaM SUBSTRATE n addmsg /kinetics/CaM-Ca4 /kinetics/CaMKII/CaMK-thr286-bind-CaM SUBSTRATE n addmsg /kinetics/CaMKII/CaMKII-thr286*-CaM /kinetics/CaMKII/CaMK-thr286-bind-CaM PRODUCT n addmsg /kinetics/CaMKII/CaMK-thr286-bind-CaM /kinetics/CaMKII/CaMKII-thr286 REAC A B addmsg /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_305 /kinetics/CaMKII/CaMKII-thr286 REAC sA B addmsg /kinetics/CaMKII/tot_autonomous_CaMKII/auton_305 /kinetics/CaMKII/CaMKII-thr286 REAC sA B addmsg /kinetics/PP1-active/Deph-thr286b /kinetics/CaMKII/CaMKII-thr286 REAC sA B addmsg /kinetics/PP1-active/Deph-thr305 /kinetics/CaMKII/CaMKII-thr286 MM_PRD pA addmsg /kinetics/CaMKII/CaMKII-CaM /kinetics/CaMKII/tot_CaM_CaMKII SUMTOTAL n nInit addmsg /kinetics/CaMKII/CaMKII-thr286*-CaM /kinetics/CaMKII/tot_CaM_CaMKII SUMTOTAL n nInit addmsg /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_305 /kinetics/CaMKII/tot_CaM_CaMKII REAC eA B addmsg /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_286 /kinetics/CaMKII/tot_CaM_CaMKII REAC eA B addmsg /kinetics/CaMKII/tot_CaM_CaMKII /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_305 ENZYME n addmsg /kinetics/CaMKII/CaMKII-thr286 /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_305 SUBSTRATE n addmsg /kinetics/CaMKII/tot_CaM_CaMKII /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_286 ENZYME n addmsg /kinetics/CaMKII/CaMKII-CaM /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_286 SUBSTRATE n addmsg /kinetics/CaMKII/CaMKII-thr286 /kinetics/CaMKII/tot_autonomous_CaMKII SUMTOTAL n nInit addmsg /kinetics/CaMKII/CaMKII*** /kinetics/CaMKII/tot_autonomous_CaMKII SUMTOTAL n nInit addmsg /kinetics/CaMKII/tot_autonomous_CaMKII/auton_305 /kinetics/CaMKII/tot_autonomous_CaMKII REAC eA B addmsg /kinetics/CaMKII/tot_autonomous_CaMKII/auton_286 /kinetics/CaMKII/tot_autonomous_CaMKII REAC eA B addmsg /kinetics/basal_CaMKII_cyt /kinetics/CaMKII/tot_autonomous_CaMKII SUMTOTAL n nInit addmsg /kinetics/CaMKII/tot_autonomous_CaMKII /kinetics/CaMKII/tot_autonomous_CaMKII/auton_305 ENZYME n addmsg /kinetics/CaMKII/CaMKII-thr286 /kinetics/CaMKII/tot_autonomous_CaMKII/auton_305 SUBSTRATE n addmsg /kinetics/CaMKII/tot_autonomous_CaMKII /kinetics/CaMKII/tot_autonomous_CaMKII/auton_286 ENZYME n addmsg /kinetics/CaMKII/CaMKII-CaM /kinetics/CaMKII/tot_autonomous_CaMKII/auton_286 SUBSTRATE n addmsg /kinetics/back_2 /kinetics/CaMKII/CaMK-thr305 REAC B A addmsg /kinetics/PP1-active/Deph-thr305a /kinetics/CaMKII/CaMK-thr305 REAC sA B addmsg /kinetics/PP1-active/Deph-thr286c /kinetics/CaMKII/CaMK-thr305 MM_PRD pA addmsg /kinetics/CaM/CaM-TR2-bind-Ca /kinetics/CaM/CaM REAC A B addmsg /kinetics/CaM/CaM /kinetics/CaM/CaM-TR2-bind-Ca SUBSTRATE n addmsg /kinetics/CaM-TR2-Ca2 /kinetics/CaM/CaM-TR2-bind-Ca PRODUCT n addmsg /kinetics/Ca /kinetics/CaM/CaM-TR2-bind-Ca SUBSTRATE n addmsg /kinetics/Ca /kinetics/CaM/CaM-TR2-bind-Ca SUBSTRATE n addmsg /kinetics/CaM-TR2-Ca2 /kinetics/CaM/CaM-TR2-Ca2-bind-Ca SUBSTRATE n addmsg /kinetics/Ca /kinetics/CaM/CaM-TR2-Ca2-bind-Ca SUBSTRATE n addmsg /kinetics/CaM-Ca3 /kinetics/CaM/CaM-TR2-Ca2-bind-Ca PRODUCT n addmsg /kinetics/CaM/CaM-TR2-bind-Ca-PSD /kinetics/CaM/CaM-PSD REAC A B addmsg /kinetics/CaM/CaM-PSD /kinetics/CaM/CaM-TR2-bind-Ca-PSD SUBSTRATE n addmsg /kinetics/CaM-TR2-Ca2-PSD /kinetics/CaM/CaM-TR2-bind-Ca-PSD PRODUCT n addmsg /kinetics/Ca-PSD /kinetics/CaM/CaM-TR2-bind-Ca-PSD SUBSTRATE n addmsg /kinetics/Ca-PSD /kinetics/CaM/CaM-TR2-bind-Ca-PSD SUBSTRATE n addmsg /kinetics/CaM-TR2-Ca2-PSD /kinetics/CaM/CaM-TR2-Ca2-bind-Ca-PSD SUBSTRATE n addmsg /kinetics/CaM-Ca3-PSD /kinetics/CaM/CaM-TR2-Ca2-bind-Ca-PSD PRODUCT n addmsg /kinetics/Ca-PSD /kinetics/CaM/CaM-TR2-Ca2-bind-Ca-PSD SUBSTRATE n addmsg /kinetics/CaM-Ca3-PSD /kinetics/CaM/CaM-Ca3-bind-Ca-PSD SUBSTRATE n addmsg /kinetics/CaM-Ca4-PSD /kinetics/CaM/CaM-Ca3-bind-Ca-PSD PRODUCT n addmsg /kinetics/Ca-PSD /kinetics/CaM/CaM-Ca3-bind-Ca-PSD SUBSTRATE n addmsg /kinetics/CaM/CaM-TR2-Ca2-bind-Ca /kinetics/CaM-Ca3 REAC B A addmsg /kinetics/CaM-Ca3-bind-Ca /kinetics/CaM-Ca3 REAC A B addmsg /kinetics/CaM/CaM-TR2-bind-Ca /kinetics/CaM-TR2-Ca2 REAC B A addmsg /kinetics/CaM/CaM-TR2-Ca2-bind-Ca /kinetics/CaM-TR2-Ca2 REAC A B addmsg /kinetics/CaNAB-Ca4/dephosph_inhib1_noCaM /kinetics/PP1/I1 MM_PRD pA addmsg /kinetics/CaM_Ca_n-CaNAB/dephosph_inhib1 /kinetics/PP1/I1 MM_PRD pA addmsg /kinetics/PP2A/PP2A-dephosph-I1 /kinetics/PP1/I1 MM_PRD pA addmsg /kinetics/PP1/dissoc-PP1-I1 /kinetics/PP1/I1 REAC B A addmsg /kinetics/PKA-active/PKA-phosph-I1 /kinetics/PP1/I1 REAC sA B addmsg /kinetics/PP1/Inact-PP1 /kinetics/PP1/I1* REAC A B addmsg /kinetics/CaNAB-Ca4/dephosph_inhib1_noCaM /kinetics/PP1/I1* REAC sA B addmsg /kinetics/CaM_Ca_n-CaNAB/dephosph_inhib1 /kinetics/PP1/I1* REAC sA B addmsg /kinetics/PP2A/PP2A-dephosph-I1 /kinetics/PP1/I1* REAC sA B addmsg /kinetics/PKA-active/PKA-phosph-I1 /kinetics/PP1/I1* MM_PRD pA addmsg /kinetics/PP1/PP1-I1* /kinetics/PP1/Inact-PP1 PRODUCT n addmsg /kinetics/PP1/I1* /kinetics/PP1/Inact-PP1 SUBSTRATE n addmsg /kinetics/PP1-active /kinetics/PP1/Inact-PP1 SUBSTRATE n addmsg /kinetics/PP1/Inact-PP1 /kinetics/PP1/PP1-I1* REAC B A addmsg /kinetics/PP2A/PP2A-dephosph-PP1-I* /kinetics/PP1/PP1-I1* REAC sA B addmsg /kinetics/CaM_Ca_n-CaNAB/dephosph-PP1-I* /kinetics/PP1/PP1-I1* REAC sA B addmsg /kinetics/PP1/dissoc-PP1-I1 /kinetics/PP1/PP1-I1 REAC A B addmsg /kinetics/PP2A/PP2A-dephosph-PP1-I* /kinetics/PP1/PP1-I1 MM_PRD pA addmsg /kinetics/CaM_Ca_n-CaNAB/dephosph-PP1-I* /kinetics/PP1/PP1-I1 MM_PRD pA addmsg /kinetics/PP1/PP1-I1 /kinetics/PP1/dissoc-PP1-I1 SUBSTRATE n addmsg /kinetics/PP1-active /kinetics/PP1/dissoc-PP1-I1 PRODUCT n addmsg /kinetics/PP1/I1 /kinetics/PP1/dissoc-PP1-I1 PRODUCT n addmsg /kinetics/PP2A/PP2A-dephosph-I1 /kinetics/PP2A REAC eA B addmsg /kinetics/PP2A/PP2A-dephosph-PP1-I* /kinetics/PP2A REAC eA B addmsg /kinetics/PP2A/PP2A-dephosph-I1_PSD /kinetics/PP2A REAC eA B addmsg /kinetics/PP2A/PP2A-dephosph-PP1-I*_PSD /kinetics/PP2A REAC eA B addmsg /kinetics/PP2A /kinetics/PP2A/PP2A-dephosph-I1 ENZYME n addmsg /kinetics/PP1/I1* /kinetics/PP2A/PP2A-dephosph-I1 SUBSTRATE n addmsg /kinetics/PP2A /kinetics/PP2A/PP2A-dephosph-PP1-I* ENZYME n addmsg /kinetics/PP1/PP1-I1* /kinetics/PP2A/PP2A-dephosph-PP1-I* SUBSTRATE n addmsg /kinetics/PP2A /kinetics/PP2A/PP2A-dephosph-I1_PSD ENZYME n addmsg /kinetics/PP1_PSD/I1* /kinetics/PP2A/PP2A-dephosph-I1_PSD SUBSTRATE n addmsg /kinetics/PP2A /kinetics/PP2A/PP2A-dephosph-PP1-I*_PSD ENZYME n addmsg /kinetics/PP1_PSD/PP1-I1* /kinetics/PP2A/PP2A-dephosph-PP1-I*_PSD SUBSTRATE n addmsg /kinetics/CaNAB-Ca4/dephosph_inhib1_noCaM /kinetics/CaNAB-Ca4 REAC eA B addmsg /kinetics/PP2B/Ca-bind-CaNAB-Ca2 /kinetics/CaNAB-Ca4 REAC B A addmsg /kinetics/PP2B/CaMCa4-bind-CaNAB /kinetics/CaNAB-Ca4 REAC A B addmsg /kinetics/CaNAB-Ca4/dephosph_inhib1_noCaM_PSD /kinetics/CaNAB-Ca4 REAC eA B addmsg /kinetics/CaNAB-Ca4 /kinetics/CaNAB-Ca4/dephosph_inhib1_noCaM ENZYME n addmsg /kinetics/PP1/I1* /kinetics/CaNAB-Ca4/dephosph_inhib1_noCaM SUBSTRATE n addmsg /kinetics/CaNAB-Ca4 /kinetics/CaNAB-Ca4/dephosph_inhib1_noCaM_PSD ENZYME n addmsg /kinetics/PP1_PSD/I1* /kinetics/CaNAB-Ca4/dephosph_inhib1_noCaM_PSD SUBSTRATE n addmsg /kinetics/PP2B/Ca-bind-CaNAB /kinetics/PP2B/CaNAB REAC A B addmsg /kinetics/PP2B/Ca-bind-CaNAB /kinetics/PP2B/CaNAB-Ca2 REAC B A addmsg /kinetics/PP2B/Ca-bind-CaNAB-Ca2 /kinetics/PP2B/CaNAB-Ca2 REAC A B addmsg /kinetics/CaNAB-Ca4 /kinetics/PP2B/Ca-bind-CaNAB-Ca2 PRODUCT n addmsg /kinetics/Ca /kinetics/PP2B/Ca-bind-CaNAB-Ca2 SUBSTRATE n addmsg /kinetics/Ca /kinetics/PP2B/Ca-bind-CaNAB-Ca2 SUBSTRATE n addmsg /kinetics/PP2B/CaNAB-Ca2 /kinetics/PP2B/Ca-bind-CaNAB-Ca2 SUBSTRATE n addmsg /kinetics/PP2B/CaNAB /kinetics/PP2B/Ca-bind-CaNAB SUBSTRATE n addmsg /kinetics/PP2B/CaNAB-Ca2 /kinetics/PP2B/Ca-bind-CaNAB PRODUCT n addmsg /kinetics/Ca /kinetics/PP2B/Ca-bind-CaNAB SUBSTRATE n addmsg /kinetics/Ca /kinetics/PP2B/Ca-bind-CaNAB SUBSTRATE n addmsg /kinetics/CaM-Ca4 /kinetics/PP2B/CaMCa4-bind-CaNAB SUBSTRATE n addmsg /kinetics/CaNAB-Ca4 /kinetics/PP2B/CaMCa4-bind-CaNAB SUBSTRATE n addmsg /kinetics/CaM_Ca_n-CaNAB /kinetics/PP2B/CaMCa4-bind-CaNAB PRODUCT n addmsg /kinetics/transloc_2 /kinetics/CaMKII-thr286-CaM-PSD REAC B A addmsg /kinetics/CaMKII-thr286-bind-CaM-PSD /kinetics/CaMKII-thr286-CaM-PSD REAC B A addmsg /kinetics/tot-CaM-CaMKII-PSD/CaM-act-286-PSD /kinetics/CaMKII-thr286-CaM-PSD MM_PRD pA addmsg /kinetics/tot-auto-PSD/auton-286-PSD /kinetics/CaMKII-thr286-CaM-PSD MM_PRD pA addmsg /kinetics/PP1-active_PSD/Deph-thr286 /kinetics/CaMKII-thr286-CaM-PSD REAC sA B addmsg /kinetics/transloc_1 /kinetics/CaMKII-CaM-PSD REAC B A addmsg /kinetics/tot-CaM-CaMKII-PSD/CaM-act-286-PSD /kinetics/CaMKII-CaM-PSD REAC sA B addmsg /kinetics/tot-auto-PSD/auton-286-PSD /kinetics/CaMKII-CaM-PSD REAC sA B addmsg /kinetics/PP1-active_PSD/Deph-thr286 /kinetics/CaMKII-CaM-PSD MM_PRD pA addmsg /kinetics/CaMKII-diss-CaM /kinetics/CaMKII-CaM-PSD REAC A B addmsg /kinetics/CaMKII-bind-CaM-PSD /kinetics/CaMKII-CaM-PSD REAC B A addmsg /kinetics/tot-CaM-CaMKII-PSD/CaM-act-305-PSD /kinetics/CaMKII-thr286-PSD REAC sA B addmsg /kinetics/tot-auto-PSD/auton-305-PSD /kinetics/CaMKII-thr286-PSD REAC sA B addmsg /kinetics/CaMKII-thr286-bind-CaM-PSD /kinetics/CaMKII-thr286-PSD REAC A B addmsg /kinetics/PP1-active_PSD/Deph-thr286b /kinetics/CaMKII-thr286-PSD REAC sA B addmsg /kinetics/PP1-active_PSD/Deph-thr305 /kinetics/CaMKII-thr286-PSD MM_PRD pA addmsg /kinetics/tot-CaM-CaMKII-PSD/CaM_act_autoph /kinetics/CaMKII-thr286-PSD MM_PRD pA addmsg /kinetics/tot-auto-PSD/auton-autoph /kinetics/CaMKII-thr286-PSD MM_PRD pA addmsg /kinetics/back_1 /kinetics/CaMKII-PSD REAC A B addmsg /kinetics/CaMKII-bind-CaM-PSD /kinetics/CaMKII-PSD REAC A B addmsg /kinetics/PP1-active_PSD/Deph-thr305a /kinetics/CaMKII-PSD MM_PRD pA addmsg /kinetics/PP1-active_PSD/Deph-thr286b /kinetics/CaMKII-PSD MM_PRD pA addmsg /kinetics/CaMKII-diss-CaM /kinetics/CaMKII-PSD REAC B A addmsg /kinetics/tot-CaM-CaMKII-PSD/CaM_act_autoph /kinetics/CaMKII-PSD REAC sA B addmsg /kinetics/tot-auto-PSD/auton-autoph /kinetics/CaMKII-PSD REAC sA B addmsg /kinetics/tot-CaM-CaMKII-PSD/CaM-act-305-PSD /kinetics/CaMKII***-PSD MM_PRD pA addmsg /kinetics/tot-auto-PSD/auton-305-PSD /kinetics/CaMKII***-PSD MM_PRD pA addmsg /kinetics/PP1-active_PSD/Deph-thr305 /kinetics/CaMKII***-PSD REAC sA B addmsg /kinetics/PP1-active_PSD/Deph-thr286c /kinetics/CaMKII***-PSD REAC sA B addmsg /kinetics/CaMKII-thr286-PSD /kinetics/tot-auto-PSD SUMTOTAL n nInit addmsg /kinetics/CaMKII***-PSD /kinetics/tot-auto-PSD SUMTOTAL n nInit addmsg /kinetics/tot-auto-PSD/auton-305-PSD /kinetics/tot-auto-PSD REAC eA B addmsg /kinetics/tot-auto-PSD/auton-286-PSD /kinetics/tot-auto-PSD REAC eA B addmsg /kinetics/basal_CaMKII_PSD /kinetics/tot-auto-PSD SUMTOTAL n nInit addmsg /kinetics/tot-auto-PSD/auton-autoph /kinetics/tot-auto-PSD REAC eA B addmsg /kinetics/tot-auto-PSD /kinetics/tot-auto-PSD/auton-305-PSD ENZYME n addmsg /kinetics/CaMKII-thr286-PSD /kinetics/tot-auto-PSD/auton-305-PSD SUBSTRATE n addmsg /kinetics/tot-auto-PSD /kinetics/tot-auto-PSD/auton-286-PSD ENZYME n addmsg /kinetics/CaMKII-CaM-PSD /kinetics/tot-auto-PSD/auton-286-PSD SUBSTRATE n addmsg /kinetics/tot-auto-PSD /kinetics/tot-auto-PSD/auton-autoph ENZYME n addmsg /kinetics/CaMKII-PSD /kinetics/tot-auto-PSD/auton-autoph SUBSTRATE n addmsg /kinetics/CaMKII-PSD /kinetics/CaMKII-bind-CaM-PSD SUBSTRATE n addmsg /kinetics/CaM-Ca4-PSD /kinetics/CaMKII-bind-CaM-PSD SUBSTRATE n addmsg /kinetics/CaMKII-CaM-PSD /kinetics/CaMKII-bind-CaM-PSD PRODUCT n addmsg /kinetics/CaMKII/CaMKII-CaM /kinetics/transloc_1 SUBSTRATE n addmsg /kinetics/CaMKII-CaM-PSD /kinetics/transloc_1 PRODUCT n addmsg /kinetics/NMDAR /kinetics/transloc_1 SUBSTRATE n addmsg /kinetics/CaMKII/CaMKII-thr286*-CaM /kinetics/transloc_2 SUBSTRATE n addmsg /kinetics/CaMKII-thr286-CaM-PSD /kinetics/transloc_2 PRODUCT n addmsg /kinetics/NMDAR /kinetics/transloc_2 SUBSTRATE n addmsg /kinetics/CaMKII-PSD /kinetics/back_1 SUBSTRATE n addmsg /kinetics/CaMKII/CaMKII /kinetics/back_1 PRODUCT n addmsg /kinetics/NMDAR /kinetics/back_1 PRODUCT n addmsg /kinetics/CaMKII-thr305-PSD /kinetics/back_2 SUBSTRATE n addmsg /kinetics/CaMKII/CaMK-thr305 /kinetics/back_2 PRODUCT n addmsg /kinetics/NMDAR /kinetics/back_2 PRODUCT n addmsg /kinetics/CaMKII-thr286-PSD /kinetics/CaMKII-thr286-bind-CaM-PSD SUBSTRATE n addmsg /kinetics/CaMKII-thr286-CaM-PSD /kinetics/CaMKII-thr286-bind-CaM-PSD PRODUCT n addmsg /kinetics/CaM-Ca4-PSD /kinetics/CaMKII-thr286-bind-CaM-PSD SUBSTRATE n addmsg /kinetics/CaM/CaM-TR2-bind-Ca-PSD /kinetics/CaM-TR2-Ca2-PSD REAC B A addmsg /kinetics/CaM/CaM-TR2-Ca2-bind-Ca-PSD /kinetics/CaM-TR2-Ca2-PSD REAC A B addmsg /kinetics/CaM/CaM-TR2-Ca2-bind-Ca-PSD /kinetics/CaM-Ca3-PSD REAC B A addmsg /kinetics/CaM/CaM-Ca3-bind-Ca-PSD /kinetics/CaM-Ca3-PSD REAC A B addmsg /kinetics/CaM/CaM-Ca3-bind-Ca-PSD /kinetics/CaM-Ca4-PSD REAC B A addmsg /kinetics/CaMKII-thr286-bind-CaM-PSD /kinetics/CaM-Ca4-PSD REAC A B addmsg /kinetics/CaMKII-bind-CaM-PSD /kinetics/CaM-Ca4-PSD REAC A B addmsg /kinetics/equilib /kinetics/CaM-Ca4-PSD REAC A B addmsg /kinetics/CaMKII-diss-CaM /kinetics/CaM-Ca4-PSD REAC B A addmsg /kinetics/CaM/CaM-TR2-bind-Ca-PSD /kinetics/Ca-PSD REAC A B addmsg /kinetics/CaM/CaM-TR2-bind-Ca-PSD /kinetics/Ca-PSD REAC A B addmsg /kinetics/CaM/CaM-TR2-Ca2-bind-Ca-PSD /kinetics/Ca-PSD REAC A B addmsg /kinetics/CaM/CaM-Ca3-bind-Ca-PSD /kinetics/Ca-PSD REAC A B addmsg /kinetics/Ca_stoch_PSD /kinetics/Ca-PSD REAC B A addmsg /kinetics/CaMKII-thr286-CaM-PSD /kinetics/286P-PSD SUMTOTAL n nInit addmsg /kinetics/CaMKII-thr286-PSD /kinetics/286P-PSD SUMTOTAL n nInit addmsg /kinetics/CaMKII-thr286-CaM-PSD /kinetics/actCaMKII-PSD SUMTOTAL n nInit addmsg /kinetics/CaMKII-CaM-PSD /kinetics/actCaMKII-PSD SUMTOTAL n nInit addmsg /kinetics/tot-auto-PSD /kinetics/actCaMKII-PSD SUMTOTAL n nInit addmsg /kinetics/actCaMKII-PSD /kinetics/tot_CaMKII_PSD SUMTOTAL n nInit addmsg /kinetics/CaMKII-PSD /kinetics/tot_CaMKII_PSD SUMTOTAL n nInit addmsg /kinetics/CaMKII-thr305-PSD /kinetics/tot_CaMKII_PSD SUMTOTAL n nInit addmsg /kinetics/CaMKII/CaMKII-CaM /kinetics/tot_CaMKII_cyt SUMTOTAL n nInit addmsg /kinetics/CaMKII/CaMKII-thr286*-CaM /kinetics/tot_CaMKII_cyt SUMTOTAL n nInit addmsg /kinetics/CaMKII/CaMKII-thr286 /kinetics/tot_CaMKII_cyt SUMTOTAL n nInit addmsg /kinetics/CaMKII/CaMKII*** /kinetics/tot_CaMKII_cyt SUMTOTAL n nInit addmsg /kinetics/CaMKII/CaMK-thr305 /kinetics/tot_CaMKII_cyt SUMTOTAL n nInit addmsg /kinetics/CaMKII/CaMKII /kinetics/tot_CaMKII_cyt SUMTOTAL n nInit addmsg /kinetics/basal_CaMKII_cyt /kinetics/tot_CaMKII_cyt SUMTOTAL n nInit addmsg /kinetics/CaM-Ca4-PSD /kinetics/equilib SUBSTRATE n addmsg /kinetics/CaM-Ca4 /kinetics/equilib PRODUCT n addmsg /kinetics/PP1_PSD/dissoc-PP1-I1 /kinetics/PP1_PSD/I1 REAC B A addmsg /kinetics/PKA-active/PKA-phosph-I1_PSD /kinetics/PP1_PSD/I1 REAC sA B addmsg /kinetics/CaM_Ca_n-CaNAB/dephosph_inhib1_PSD /kinetics/PP1_PSD/I1 MM_PRD pA addmsg /kinetics/PP2A/PP2A-dephosph-I1_PSD /kinetics/PP1_PSD/I1 MM_PRD pA addmsg /kinetics/CaNAB-Ca4/dephosph_inhib1_noCaM_PSD /kinetics/PP1_PSD/I1 MM_PRD pA addmsg /kinetics/Inact-PP1 /kinetics/PP1_PSD/I1* REAC A B addmsg /kinetics/PKA-active/PKA-phosph-I1_PSD /kinetics/PP1_PSD/I1* MM_PRD pA addmsg /kinetics/CaM_Ca_n-CaNAB/dephosph_inhib1_PSD /kinetics/PP1_PSD/I1* REAC sA B addmsg /kinetics/PP2A/PP2A-dephosph-I1_PSD /kinetics/PP1_PSD/I1* REAC sA B addmsg /kinetics/CaNAB-Ca4/dephosph_inhib1_noCaM_PSD /kinetics/PP1_PSD/I1* REAC sA B addmsg /kinetics/Inact-PP1 /kinetics/PP1_PSD/PP1-I1* REAC B A addmsg /kinetics/CaM_Ca_n-CaNAB/dephosph-PP1-I*_PSD /kinetics/PP1_PSD/PP1-I1* REAC sA B addmsg /kinetics/PP2A/PP2A-dephosph-PP1-I*_PSD /kinetics/PP1_PSD/PP1-I1* REAC sA B addmsg /kinetics/CaM_Ca_n-CaNAB/dephosph-PP1-I*_PSD /kinetics/PP1_PSD/PP1-I1 MM_PRD pA addmsg /kinetics/PP2A/PP2A-dephosph-PP1-I*_PSD /kinetics/PP1_PSD/PP1-I1 MM_PRD pA addmsg /kinetics/PP1_PSD/dissoc-PP1-I1 /kinetics/PP1_PSD/PP1-I1 REAC A B addmsg /kinetics/PP1_PSD/I1 /kinetics/PP1_PSD/dissoc-PP1-I1 PRODUCT n addmsg /kinetics/PP1-active_PSD /kinetics/PP1_PSD/dissoc-PP1-I1 PRODUCT n addmsg /kinetics/PP1_PSD/PP1-I1 /kinetics/PP1_PSD/dissoc-PP1-I1 SUBSTRATE n addmsg /kinetics/PP1_PSD/I1* /kinetics/Inact-PP1 SUBSTRATE n addmsg /kinetics/PP1_PSD/PP1-I1* /kinetics/Inact-PP1 PRODUCT n addmsg /kinetics/PP1-active_PSD /kinetics/Inact-PP1 SUBSTRATE n addmsg /kinetics/PP1-active_PSD/Deph-thr286 /kinetics/PP1-active_PSD REAC eA B addmsg /kinetics/PP1-active_PSD/Deph-thr286b /kinetics/PP1-active_PSD REAC eA B addmsg /kinetics/PP1-active_PSD/Deph-thr305 /kinetics/PP1-active_PSD REAC eA B addmsg /kinetics/PP1-active_PSD/Deph-thr305a /kinetics/PP1-active_PSD REAC eA B addmsg /kinetics/PP1-active_PSD/Deph-thr286c /kinetics/PP1-active_PSD REAC eA B addmsg /kinetics/PP1_PSD/dissoc-PP1-I1 /kinetics/PP1-active_PSD REAC B A addmsg /kinetics/Inact-PP1 /kinetics/PP1-active_PSD REAC A B addmsg /kinetics/PP1-active_PSD /kinetics/PP1-active_PSD/Deph-thr286 ENZYME n addmsg /kinetics/CaMKII-thr286-CaM-PSD /kinetics/PP1-active_PSD/Deph-thr286 SUBSTRATE n addmsg /kinetics/PP1-active_PSD /kinetics/PP1-active_PSD/Deph-thr286b ENZYME n addmsg /kinetics/CaMKII-thr286-PSD /kinetics/PP1-active_PSD/Deph-thr286b SUBSTRATE n addmsg /kinetics/PP1-active_PSD /kinetics/PP1-active_PSD/Deph-thr305 ENZYME n addmsg /kinetics/CaMKII***-PSD /kinetics/PP1-active_PSD/Deph-thr305 SUBSTRATE n addmsg /kinetics/PP1-active_PSD /kinetics/PP1-active_PSD/Deph-thr286c ENZYME n addmsg /kinetics/CaMKII***-PSD /kinetics/PP1-active_PSD/Deph-thr286c SUBSTRATE n addmsg /kinetics/PP1-active_PSD /kinetics/PP1-active_PSD/Deph-thr305a ENZYME n addmsg /kinetics/CaMKII-thr305-PSD /kinetics/PP1-active_PSD/Deph-thr305a SUBSTRATE n addmsg /kinetics/CaM-Ca3 /kinetics/CaM-Ca3-bind-Ca SUBSTRATE n addmsg /kinetics/Ca /kinetics/CaM-Ca3-bind-Ca SUBSTRATE n addmsg /kinetics/CaM-Ca4 /kinetics/CaM-Ca3-bind-Ca PRODUCT n addmsg /kinetics/CaMKII/tot_CaM_CaMKII /kinetics/act_CaMKII_cyt SUMTOTAL n nInit addmsg /kinetics/CaMKII/tot_autonomous_CaMKII /kinetics/act_CaMKII_cyt SUMTOTAL n nInit addmsg /kinetics/transloc_2 /kinetics/NMDAR REAC A B addmsg /kinetics/transloc_1 /kinetics/NMDAR REAC A B addmsg /kinetics/back_1 /kinetics/NMDAR REAC B A addmsg /kinetics/back_2 /kinetics/NMDAR REAC B A addmsg /kinetics/CaMKII-CaM-PSD /kinetics/CaMKII-diss-CaM SUBSTRATE n addmsg /kinetics/CaM-Ca4-PSD /kinetics/CaMKII-diss-CaM PRODUCT n addmsg /kinetics/CaMKII-PSD /kinetics/CaMKII-diss-CaM PRODUCT n addmsg /kinetics/CaM_Ca_n-CaNAB/dephosph_inhib1 /kinetics/CaM_Ca_n-CaNAB REAC eA B addmsg /kinetics/CaM_Ca_n-CaNAB/dephosph-PP1-I* /kinetics/CaM_Ca_n-CaNAB REAC eA B addmsg /kinetics/CaM_Ca_n-CaNAB/dephosph_inhib1_PSD /kinetics/CaM_Ca_n-CaNAB REAC eA B addmsg /kinetics/CaM_Ca_n-CaNAB/dephosph-PP1-I*_PSD /kinetics/CaM_Ca_n-CaNAB REAC eA B addmsg /kinetics/PP2B/CaMCa4-bind-CaNAB /kinetics/CaM_Ca_n-CaNAB REAC B A addmsg /kinetics/CaM_Ca_n-CaNAB /kinetics/CaM_Ca_n-CaNAB/dephosph_inhib1 ENZYME n addmsg /kinetics/PP1/I1* /kinetics/CaM_Ca_n-CaNAB/dephosph_inhib1 SUBSTRATE n addmsg /kinetics/CaM_Ca_n-CaNAB /kinetics/CaM_Ca_n-CaNAB/dephosph-PP1-I* ENZYME n addmsg /kinetics/PP1/PP1-I1* /kinetics/CaM_Ca_n-CaNAB/dephosph-PP1-I* SUBSTRATE n addmsg /kinetics/CaM_Ca_n-CaNAB /kinetics/CaM_Ca_n-CaNAB/dephosph_inhib1_PSD ENZYME n addmsg /kinetics/PP1_PSD/I1* /kinetics/CaM_Ca_n-CaNAB/dephosph_inhib1_PSD SUBSTRATE n addmsg /kinetics/CaM_Ca_n-CaNAB /kinetics/CaM_Ca_n-CaNAB/dephosph-PP1-I*_PSD ENZYME n addmsg /kinetics/PP1_PSD/PP1-I1* /kinetics/CaM_Ca_n-CaNAB/dephosph-PP1-I*_PSD SUBSTRATE n addmsg /kinetics/Stoch_Basal_CaMKII_PSD /kinetics/basal_CaMKII_PSD REAC B A addmsg /kinetics/Ca_stoch_cyt /kinetics/Ca_control_cyt REAC A B addmsg /kinetics/Ca_control_cyt /kinetics/Ca_stoch_cyt SUBSTRATE n addmsg /kinetics/Ca /kinetics/Ca_stoch_cyt PRODUCT n addmsg /kinetics/Ca_stoch_PSD /kinetics/Ca_control_PSD REAC A B addmsg /kinetics/Ca_control_PSD /kinetics/Ca_stoch_PSD SUBSTRATE n addmsg /kinetics/Ca-PSD /kinetics/Ca_stoch_PSD PRODUCT n addmsg /kinetics/Stoch_Basal_CaMKII_PSD /kinetics/basal_CaMKII_PSD_control REAC A B addmsg /kinetics/basal_CaMKII_PSD_control /kinetics/Stoch_Basal_CaMKII_PSD SUBSTRATE n addmsg /kinetics/basal_CaMKII_PSD /kinetics/Stoch_Basal_CaMKII_PSD PRODUCT n addmsg /kinetics/CaMKII-thr286-CaM-PSD /kinetics/tot-CaM-CaMKII-PSD SUMTOTAL n nInit addmsg /kinetics/CaMKII-CaM-PSD /kinetics/tot-CaM-CaMKII-PSD SUMTOTAL n nInit addmsg /kinetics/tot-CaM-CaMKII-PSD/CaM-act-305-PSD /kinetics/tot-CaM-CaMKII-PSD REAC eA B addmsg /kinetics/tot-CaM-CaMKII-PSD/CaM-act-286-PSD /kinetics/tot-CaM-CaMKII-PSD REAC eA B addmsg /kinetics/tot-CaM-CaMKII-PSD/CaM_act_autoph /kinetics/tot-CaM-CaMKII-PSD REAC eA B addmsg /kinetics/tot-CaM-CaMKII-PSD /kinetics/tot-CaM-CaMKII-PSD/CaM-act-305-PSD ENZYME n addmsg /kinetics/CaMKII-thr286-PSD /kinetics/tot-CaM-CaMKII-PSD/CaM-act-305-PSD SUBSTRATE n addmsg /kinetics/tot-CaM-CaMKII-PSD /kinetics/tot-CaM-CaMKII-PSD/CaM-act-286-PSD ENZYME n addmsg /kinetics/CaMKII-CaM-PSD /kinetics/tot-CaM-CaMKII-PSD/CaM-act-286-PSD SUBSTRATE n addmsg /kinetics/tot-CaM-CaMKII-PSD /kinetics/tot-CaM-CaMKII-PSD/CaM_act_autoph ENZYME n addmsg /kinetics/CaMKII-PSD /kinetics/tot-CaM-CaMKII-PSD/CaM_act_autoph SUBSTRATE n addmsg /kinetics/PKC-control /kinetics/PKC-stoch-input SUBSTRATE n addmsg /kinetics/PKC-active /kinetics/PKC-stoch-input PRODUCT n addmsg /kinetics/AC/AC2*/kenz /kinetics/cAMP MM_PRD pA addmsg /kinetics/AC/AC1-CaM/kenz /kinetics/cAMP MM_PRD pA addmsg /kinetics/AC/cAMP-PDE*/PDE* /kinetics/cAMP REAC sA B addmsg /kinetics/AC/cAMP-PDE/PDE /kinetics/cAMP REAC sA B addmsg /kinetics/AC/PDE1/PDE1 /kinetics/cAMP REAC sA B addmsg /kinetics/AC/CaM.PDE1/CaM.PDE1 /kinetics/cAMP REAC sA B addmsg /kinetics/AC/cAMP_diffusion /kinetics/cAMP REAC A B addmsg /kinetics/PKA/cAMP-bind-site-B1 /kinetics/cAMP REAC A B addmsg /kinetics/PKA/cAMP-bind-site-B2 /kinetics/cAMP REAC A B addmsg /kinetics/PKA/cAMP-bind-site-A1 /kinetics/cAMP REAC A B addmsg /kinetics/PKA/cAMP-bind-site-A2 /kinetics/cAMP REAC A B addmsg /kinetics/AC/AC2*/kenz /kinetics/AC/ATP REAC sA B addmsg /kinetics/AC/AC1-CaM/kenz /kinetics/AC/ATP REAC sA B addmsg /kinetics/AC/CaM-bind-AC1 /kinetics/AC/AC1-CaM REAC B A addmsg /kinetics/AC/AC1-CaM /kinetics/AC/AC1-CaM/kenz ENZYME n addmsg /kinetics/AC/ATP /kinetics/AC/AC1-CaM/kenz SUBSTRATE n addmsg /kinetics/AC/CaM-bind-AC1 /kinetics/AC/AC1 REAC A B addmsg /kinetics/CaM-Ca4 /kinetics/AC/CaM-bind-AC1 SUBSTRATE n addmsg /kinetics/AC/AC1-CaM /kinetics/AC/CaM-bind-AC1 PRODUCT n addmsg /kinetics/AC/AC1 /kinetics/AC/CaM-bind-AC1 SUBSTRATE n addmsg /kinetics/AC/dephosph-AC2 /kinetics/AC/AC2* REAC A B addmsg /kinetics/PKC-active/phosph-AC2 /kinetics/AC/AC2* MM_PRD pA addmsg /kinetics/AC/AC2* /kinetics/AC/AC2*/kenz ENZYME n addmsg /kinetics/AC/ATP /kinetics/AC/AC2*/kenz SUBSTRATE n addmsg /kinetics/AC/dephosph-AC2 /kinetics/AC/AC2 REAC B A addmsg /kinetics/PKC-active/phosph-AC2 /kinetics/AC/AC2 REAC sA B addmsg /kinetics/AC/AC2* /kinetics/AC/dephosph-AC2 SUBSTRATE n addmsg /kinetics/AC/AC2 /kinetics/AC/dephosph-AC2 PRODUCT n addmsg /kinetics/AC/cAMP-PDE*/PDE* /kinetics/AC/AMP MM_PRD pA addmsg /kinetics/AC/cAMP-PDE/PDE /kinetics/AC/AMP MM_PRD pA addmsg /kinetics/AC/CaM.PDE1/CaM.PDE1 /kinetics/AC/AMP MM_PRD pA addmsg /kinetics/AC/PDE1/PDE1 /kinetics/AC/AMP MM_PRD pA addmsg /kinetics/AC/cAMP-PDE/PDE /kinetics/AC/cAMP-PDE REAC eA B addmsg /kinetics/AC/dephosph-PDE /kinetics/AC/cAMP-PDE REAC B A addmsg /kinetics/PKA-active/phosph-PDE /kinetics/AC/cAMP-PDE REAC sA B addmsg /kinetics/AC/cAMP-PDE /kinetics/AC/cAMP-PDE/PDE ENZYME n addmsg /kinetics/cAMP /kinetics/AC/cAMP-PDE/PDE SUBSTRATE n addmsg /kinetics/AC/cAMP-PDE*/PDE* /kinetics/AC/cAMP-PDE* REAC eA B addmsg /kinetics/AC/dephosph-PDE /kinetics/AC/cAMP-PDE* REAC A B addmsg /kinetics/PKA-active/phosph-PDE /kinetics/AC/cAMP-PDE* MM_PRD pA addmsg /kinetics/AC/cAMP-PDE* /kinetics/AC/cAMP-PDE*/PDE* ENZYME n addmsg /kinetics/cAMP /kinetics/AC/cAMP-PDE*/PDE* SUBSTRATE n addmsg /kinetics/AC/cAMP-PDE* /kinetics/AC/dephosph-PDE SUBSTRATE n addmsg /kinetics/AC/cAMP-PDE /kinetics/AC/dephosph-PDE PRODUCT n addmsg /kinetics/AC/PDE1/PDE1 /kinetics/AC/PDE1 REAC eA B addmsg /kinetics/AC/CaM_bind_PDE1 /kinetics/AC/PDE1 REAC A B addmsg /kinetics/AC/PDE1 /kinetics/AC/PDE1/PDE1 ENZYME n addmsg /kinetics/cAMP /kinetics/AC/PDE1/PDE1 SUBSTRATE n addmsg /kinetics/AC/CaM.PDE1/CaM.PDE1 /kinetics/AC/CaM.PDE1 REAC eA B addmsg /kinetics/AC/CaM_bind_PDE1 /kinetics/AC/CaM.PDE1 REAC B A addmsg /kinetics/AC/CaM.PDE1 /kinetics/AC/CaM.PDE1/CaM.PDE1 ENZYME n addmsg /kinetics/cAMP /kinetics/AC/CaM.PDE1/CaM.PDE1 SUBSTRATE n addmsg /kinetics/AC/PDE1 /kinetics/AC/CaM_bind_PDE1 SUBSTRATE n addmsg /kinetics/AC/CaM.PDE1 /kinetics/AC/CaM_bind_PDE1 PRODUCT n addmsg /kinetics/CaM-Ca4 /kinetics/AC/CaM_bind_PDE1 SUBSTRATE n addmsg /kinetics/AC/cAMP_diffusion /kinetics/AC/cAMP_in_dend REAC B A addmsg /kinetics/cAMP /kinetics/AC/cAMP_diffusion SUBSTRATE n addmsg /kinetics/AC/cAMP_in_dend /kinetics/AC/cAMP_diffusion PRODUCT n addmsg /kinetics/PKC-stoch-input /kinetics/PKC-control REAC A B addmsg /kinetics/PKA/cAMP-bind-site-B1 /kinetics/PKA/R2C2 REAC A B addmsg /kinetics/PKA/cAMP-bind-site-B1 /kinetics/PKA/R2C2-cAMP REAC B A addmsg /kinetics/PKA/cAMP-bind-site-B2 /kinetics/PKA/R2C2-cAMP REAC A B addmsg /kinetics/PKA/R2C2 /kinetics/PKA/cAMP-bind-site-B1 SUBSTRATE n addmsg /kinetics/PKA/R2C2-cAMP /kinetics/PKA/cAMP-bind-site-B1 PRODUCT n addmsg /kinetics/cAMP /kinetics/PKA/cAMP-bind-site-B1 SUBSTRATE n addmsg /kinetics/PKA/R2C2-cAMP /kinetics/PKA/cAMP-bind-site-B2 SUBSTRATE n addmsg /kinetics/cAMP /kinetics/PKA/cAMP-bind-site-B2 SUBSTRATE n addmsg /kinetics/PKA/R2C2-cAMP2 /kinetics/PKA/cAMP-bind-site-B2 PRODUCT n addmsg /kinetics/PKA/R2C2-cAMP2 /kinetics/PKA/cAMP-bind-site-A1 SUBSTRATE n addmsg /kinetics/cAMP /kinetics/PKA/cAMP-bind-site-A1 SUBSTRATE n addmsg /kinetics/PKA/R2C2-cAMP3 /kinetics/PKA/cAMP-bind-site-A1 PRODUCT n addmsg /kinetics/cAMP /kinetics/PKA/cAMP-bind-site-A2 SUBSTRATE n addmsg /kinetics/PKA/R2C2-cAMP3 /kinetics/PKA/cAMP-bind-site-A2 SUBSTRATE n addmsg /kinetics/PKA/R2C2-cAMP4 /kinetics/PKA/cAMP-bind-site-A2 PRODUCT n addmsg /kinetics/PKA/cAMP-bind-site-B2 /kinetics/PKA/R2C2-cAMP2 REAC B A addmsg /kinetics/PKA/cAMP-bind-site-A1 /kinetics/PKA/R2C2-cAMP2 REAC A B addmsg /kinetics/PKA/cAMP-bind-site-A1 /kinetics/PKA/R2C2-cAMP3 REAC B A addmsg /kinetics/PKA/cAMP-bind-site-A2 /kinetics/PKA/R2C2-cAMP3 REAC A B addmsg /kinetics/PKA/cAMP-bind-site-A2 /kinetics/PKA/R2C2-cAMP4 REAC B A addmsg /kinetics/PKA/Release-C1 /kinetics/PKA/R2C2-cAMP4 REAC A B addmsg /kinetics/PKA/Release-C1 /kinetics/PKA/R2C-cAMP4 REAC B A addmsg /kinetics/PKA/Release-C2 /kinetics/PKA/R2C-cAMP4 REAC A B addmsg /kinetics/PKA/Release-C2 /kinetics/PKA/R2-cAMP4 REAC B A addmsg /kinetics/PKA/R2C2-cAMP4 /kinetics/PKA/Release-C1 SUBSTRATE n addmsg /kinetics/PKA-active /kinetics/PKA/Release-C1 PRODUCT n addmsg /kinetics/PKA/R2C-cAMP4 /kinetics/PKA/Release-C1 PRODUCT n addmsg /kinetics/PKA/R2C-cAMP4 /kinetics/PKA/Release-C2 SUBSTRATE n addmsg /kinetics/PKA-active /kinetics/PKA/Release-C2 PRODUCT n addmsg /kinetics/PKA/R2-cAMP4 /kinetics/PKA/Release-C2 PRODUCT n addmsg /kinetics/PKA/inhib-PKA /kinetics/PKA/PKA-inhibitor REAC A B addmsg /kinetics/PKA-active /kinetics/PKA/inhib-PKA SUBSTRATE n addmsg /kinetics/PKA/PKA-inhibitor /kinetics/PKA/inhib-PKA SUBSTRATE n addmsg /kinetics/PKA/inhibited-PKA /kinetics/PKA/inhib-PKA PRODUCT n addmsg /kinetics/PKA/inhib-PKA /kinetics/PKA/inhibited-PKA REAC B A addmsg /kinetics/PKC-active/phosph-AC2 /kinetics/PKC-active REAC eA B addmsg /kinetics/PKC-stoch-input /kinetics/PKC-active REAC B A addmsg /kinetics/PKC-active /kinetics/PKC-active/phosph-AC2 ENZYME n addmsg /kinetics/AC/AC2 /kinetics/PKC-active/phosph-AC2 SUBSTRATE n addmsg /kinetics/back_2 /kinetics/CaMKII-thr305-PSD REAC A B addmsg /kinetics/PP1-active_PSD/Deph-thr305a /kinetics/CaMKII-thr305-PSD REAC sA B addmsg /kinetics/PP1-active_PSD/Deph-thr286c /kinetics/CaMKII-thr305-PSD MM_PRD pA addmsg /kinetics/actCaMKII-PSD /graphs/conc1/actCaMKII-PSD.Co PLOT Co *actCaMKII-PSD.Co *12 addmsg /kinetics/tot_CaMKII_PSD /graphs/conc1/tot_CaMKII_PSD.Co PLOT Co *tot_CaMKII_PSD.Co *23 addmsg /kinetics/act_CaMKII_cyt /graphs/conc1/act_CaMKII_cyt.Co PLOT Co *act_CaMKII_cyt.Co *14 addmsg /kinetics/tot_CaMKII_cyt /graphs/conc1/tot_CaMKII_cyt.Co PLOT Co *tot_CaMKII_cyt.Co *24 addmsg /kinetics/CaM_Ca_n-CaNAB /graphs/conc1/CaM_Ca_n-CaNAB.Co PLOT Co *CaM_Ca_n-CaNAB.Co *1 addmsg /kinetics/CaM-Ca4-PSD /graphs/conc2/CaM-Ca4-PSD.Co PLOT Co *CaM-Ca4-PSD.Co *blue addmsg /kinetics/PP1-active_PSD /moregraphs/conc3/PP1-active_PSD.Co PLOT Co *PP1-active_PSD.Co *cyan addmsg /kinetics/PKA-active /moregraphs/conc3/PKA-active.Co PLOT Co *PKA-active.Co *yellow addmsg /kinetics/Ca /moregraphs/conc3/Ca.Co PLOT Co *Ca.Co *red addmsg /kinetics/PP1-active /moregraphs/conc4/PP1-active.Co PLOT Co *PP1-active.Co *cyan addmsg /kinetics/CaM-Ca4 /moregraphs/conc4/CaM-Ca4.Co PLOT Co *CaM-Ca4.Co *blue enddump // End of dump call /kinetics/PP1-active/notes LOAD \ "Cohen et al Meth Enz 159 390-408 is main source of info" \ "conc = 1.8 uM" call /kinetics/PKA-active/PKA-phosph-I1/notes LOAD \ "#s from Bramson et al CRC crit rev Biochem" \ "15:2 93-124. They have a huge list of peptide substrates" \ "and I have chosen high-ish rates." \ "These consts give too much PKA activity, so lower Vmax 1/3." \ "Now, k1 = 3e-5, k2 = 36, k3 = 9 (still pretty fast)." \ "Also lower Km 1/3 so k1 = 1e-5" \ "Cohen et al FEBS Lett 76:182-86 1977 say rate =30% PKA act on " \ "phosphokinase beta." \ "" call /kinetics/PKA-active/phosph-PDE/notes LOAD \ "Same rates as PKA-phosph-I1" call /kinetics/CaMKII/notes LOAD \ "Main reference here is the review by Hanson and Schulman, Ann Rev Biochem" \ "1992 vol 61 pp 559-601. Most of the mechanistic details and a few constants" \ "are derived from there. Many kinetics are from Hanson and Schulman JBC" \ "267:24 17216-17224 1992." \ "The enzs look a terrible mess. Actually it is just 3 reactions for diff sites," \ "by 4 states of CaMKII, defined by the phosph state." call /kinetics/CaMKII/CaMKII/notes LOAD \ "Huge conc of CaMKII. In PSD it is 20-40% of protein, so we assume it is around" \ "2.5% of protein in spine as a whole. This level is so high it is unlikely to matter" \ "much if we are off a bit." call /kinetics/CaMKII/CaMKII-thr286*-CaM/notes LOAD \ "From Hanson and Schulman, the thr286 is responsible for autonomous activation" \ "of CaMKII." call /kinetics/CaMKII/CaMKII***/notes LOAD \ "From Hanson and Schulman, the CaMKII does a lot of autophosphorylation" \ "just after the CaM is released. This prevents further CaM binding and renders" \ "the enzyme quite independent of Ca." call /kinetics/CaMKII/CaMKII-bind-CaM/notes LOAD \ "This is tricky. There is some cooperativity here arising from interactions" \ "between the subunits of the CAMKII holoenzyme. However, the" \ "stoichiometry is 1. " \ "Kb/Kf = 6e4 #/cell. Rate is fast (see Hanson et al Neuron 12 943-956 1994)" \ "so lets say kb = 10. This gives kf = 1.6667e-4" \ "H&S AnnRev Biochem 92 give tau for dissoc as 0.2 sec at low Ca, 0.4 at high." \ "Low Ca = 100 nM = physiol." call /kinetics/CaMKII/CaMK-thr286-bind-CaM/notes LOAD \ "Affinity is up 1000X. Time to release is about 20 sec, so the kb is OK at 0.1" \ "This makes Kf around 1.6666e-3" \ "" call /kinetics/CaMKII/CaMKII-thr286/notes LOAD \ "I am not sure if we need to endow this one with a lot of enzs. It is likely" \ "to be a short-lived intermediate, since it will be phosphorylated further" \ "as soon as the CAM falls off." call /kinetics/CaMKII/tot_CaM_CaMKII/CaM_act_305/notes LOAD \ "Rates from autocamtide phosphorylation, from " \ "Hanson and Schulman JBC 267:24 17216-17224 1992." \ "Jan 1 1998: Speed up 12x to match fig 5." call /kinetics/CaMKII/tot_autonomous_CaMKII/auton_305/notes LOAD \ "See Hanson and Schulman again, for afterburst rates of" \ "phosph." call /kinetics/CaMKII/CaMK-thr305/notes LOAD \ "This forms due to basal autophosphorylation, but I think it has to be" \ "considered as a pathway even if some CaM is floating around. In either" \ "case it will tend to block further binding of CaM, and will not display any" \ "enzyme activity. See Hanson and Schulman JBC 267:24 pp17216-17224 1992" 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-TR2-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 !)...." call /kinetics/CaM/CaM-TR2-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-PSD/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-TR2-bind-Ca-PSD/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 !)...." call /kinetics/CaM/CaM-TR2-Ca2-bind-Ca-PSD/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-Ca3-bind-Ca-PSD/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-TR2-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/PP1/I1/notes LOAD \ "I1 is a 'mixed' inhibitor, but at high enz concs it looks like a non-compet" \ "inhibitor (Foulkes et al Eur J Biochem 132 309-313 9183)." \ "We treat it as non-compet, so it just turns the enz off" \ "without interacting with the binding site." \ "Cohen et al ann rev bioch refer to results where conc is " \ "1.5 to 1.8 uM. In order to get complete inhib of PP1, which is at 1.8 uM," \ "we need >= 1.8 uM." \ "" \ "" call /kinetics/PP1/I1*/notes LOAD \ "Dephosph is mainly by PP2B" call /kinetics/PP1/Inact-PP1/notes LOAD \ "K inhib = 1nM from Cohen Ann Rev Bioch 1989, " \ "4 nM from Foukes et al " \ "Assume 2 nM. kf /kb = 8.333e-4" call /kinetics/PP1/dissoc-PP1-I1/notes LOAD \ "Let us assume that the equil in this case is very far over to the" \ "right. This is probably safe." \ "" call /kinetics/PP2A/PP2A-dephosph-I1/notes LOAD \ "PP2A does most of the dephosph of I1 at basal Ca levels. See" \ "the review by Cohen in Ann Rev Biochem 1989." \ "For now, lets halve Km. k1 was 3.3e-6, now 6.6e-6" \ "" call /kinetics/PP2A/PP2A-dephosph-PP1-I*/notes LOAD \ "k1 changed from 3.3e-6 to 6.6e-6" \ "" call /kinetics/PP2A/PP2A-dephosph-I1_PSD/notes LOAD \ "PP2A does most of the dephosph of I1 at basal Ca levels. See" \ "the review by Cohen in Ann Rev Biochem 1989." \ "For now, lets halve Km. k1 was 3.3e-6, now 6.6e-6" \ "" call /kinetics/PP2A/PP2A-dephosph-PP1-I*_PSD/notes LOAD \ "k1 changed from 3.3e-6 to 6.6e-6" \ "" call /kinetics/CaNAB-Ca4/dephosph_inhib1_noCaM/notes LOAD \ "The rates here are so slow I do not know if we should even bother" \ "with this enz reacn. These numbers are from Liu and Storm." \ "Other refs suggest that the Km stays the same" \ "but the Vmax goes to 10% of the CaM stim levels. " \ "Prev: k1=2.2e-9, k2 = 0.0052, k3 = 0.0013" \ "New : k1=5.7e-8, k2=.136, k3=.034" call /kinetics/CaNAB-Ca4/dephosph_inhib1_noCaM_PSD/notes LOAD \ "The rates here are so slow I do not know if we should even bother" \ "with this enz reacn. These numbers are from Liu and Storm." \ "Other refs suggest that the Km stays the same" \ "but the Vmax goes to 10% of the CaM stim levels. " \ "Prev: k1=2.2e-9, k2 = 0.0052, k3 = 0.0013" \ "New : k1=5.7e-8, k2=.136, k3=.034" call /kinetics/PP2B/notes LOAD \ "Also called Calcineurin." \ "Major sources of info:" \ "Cohen, P Ann Rev Biochem 1989 58:453-508" \ "Mumby and Walker Physiol Rev 73:4 673-699" \ "Stemmer and Klee Biochem 33 1994 6859-6866" \ "Liu and Storm JBC 264:22 1989 12800-12804" \ "This model is unusual: There is actually more expt info than I want to" \ "put in the model at this time." \ "Phosph: Hashimoto and Soderling JBC 1989 264:28 16624-16629 (Not used)" call /kinetics/PP2B/CaNAB/notes LOAD \ "We assume that the A and B subunits of PP2B are always bound under" \ "physiol conditions." \ "Up to 1% of brain protein = 25 uM. I need to work out how it is distributed" \ "between cytosolic and particulate fractions." \ "Tallant and Cheung '83 Biochem 22 3630-3635 have conc in many " \ "species, average for mammalian brain is around 1 uM." call /kinetics/PP2B/Ca-bind-CaNAB-Ca2/notes LOAD \ "This process is probably much more complicated and involves CaM." \ "However, as I can't find detailed info I am bundling this into a" \ "single step." \ "Based on Steemer and Klee pg 6863, the Kact is 0.5 uM." \ "kf/kb = 1/(0.5 * 6e5)^2 = 1.11e-11" call /kinetics/PP2B/Ca-bind-CaNAB/notes LOAD \ "going on the experience with CaM, we put the fast (high affinity)" \ "sites first. We only know (Stemmer and Klee) that the affinity is < 70 nM." \ "Assuming 10 nM at first, we get" \ "kf = 2.78e-8, kb = 1." \ "Try 20 nM." \ "kf = 7e-9, kb = 1" \ call /kinetics/transloc_1/notes LOAD \ "Rates to match curve in fig2 from Shen and Meyer, " \ "Science 284:162-166(1999)," \ "calculated for 6:1 alpha:beta CaMKII heterodimers" \ "" call /kinetics/transloc_2/notes LOAD \ "Same as for transloc_1" \ "" \ "" \ "" call /kinetics/back_1/notes LOAD \ "Rates set by the translocation experiments of " \ "Shen and Meyer, Science 1999." call /kinetics/back_2/notes LOAD \ "Same as for back_1" \ "" call /kinetics/CaMKII-thr286-bind-CaM-PSD/notes LOAD \ "Same values as for the main compartment" \ "Can the main compartment pool of Ca/CaM be used?" call /kinetics/CaM-TR2-Ca2-PSD/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/equilib/notes LOAD \ "Diffusional equilibrium between PSD- and cytosolic compartment." \ "According to D. Bary in Cell Movements 2nd ed 2001 D for proteins" \ "is 5e-7 cm^2/s giving 10 ms for a translocation of 1 um. " call /kinetics/PP1_PSD/I1/notes LOAD \ "I1 is a 'mixed' inhibitor, but at high enz concs it looks like a non-compet" \ "inhibitor (Foulkes et al Eur J Biochem 132 309-313 9183)." \ "We treat it as non-compet, so it just turns the enz off" \ "without interacting with the binding site." \ "Cohen et al ann rev bioch refer to results where conc is " \ "1.5 to 1.8 uM. In order to get complete inhib of PP1, which is at 1.8 uM," \ "we need >= 1.8 uM." \ "" \ "" call /kinetics/PP1_PSD/I1*/notes LOAD \ "Dephosph is mainly by PP2B" call /kinetics/PP1_PSD/dissoc-PP1-I1/notes LOAD \ "Let us assume that the equil in this case is very far over to the" \ "right. This is probably safe." \ "" call /kinetics/Inact-PP1/notes LOAD \ "K inhib = 1nM from Cohen Ann Rev Bioch 1989, " \ "4 nM from Foukes et al " \ "Assume 2 nM. kf /kb = 8.333e-4" call /kinetics/PP1-active_PSD/notes LOAD \ "Cohen et al Meth Enz 159 390-408 is main source of info" \ "conc = 1.8 uM" call /kinetics/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/NMDAR/notes LOAD \ "The stochiometry is a bit off here. Each NMDAR actually" \ "binds to a holoenzyme, about 12 CaMKII subunits. But" \ "our CaMKII calculations are in terms of individual" \ "subunits. So as a hack, we put in much more NMDAR than" \ "is actually there." call /kinetics/cAMP/notes LOAD \ "The conc of this has been a problem. Schaecter and Benowitz use 50 uM," \ "but Shinomura et al have < 5. So I have altered the cAMP-dependent " \ "rates in the PKA model to reflect this." call /kinetics/AC/ATP/notes LOAD \ "ATP is present in all cells between 2 and 10 mM. See Lehninger" \ "" call /kinetics/AC/AC1-CaM/notes LOAD \ "This version of cyclase is Calmodulin activated." \ "Gs stims it but betagamma inhibits." call /kinetics/AC/AC1-CaM/kenz/notes LOAD \ "17 Feb 2005" \ "Halved Vmax as the amount of enzyme has been doubled to" \ "get an integer value in the spine." \ "18 Feb 2005. Updated Km from BRENDA: EC No 4.6.1.1" \ "Rat Km: 0.95 mM Turnover 12/sec." \ "Human Km: 0.3 mM" \ "" \ "12 umol/min/mg for mammalia, turnover is 12/sec" \ "See PMID 8663304 by Dessauer and Gilman JBC 271 1996" \ "" \ "Unfortunately turnover range is from 34 down to 0.1" \ "in different studies, according to BRENDA." \ "" call /kinetics/AC/AC1/notes LOAD \ "Starting conc at 20 nM." \ "Reduced conc to 10 nM, 14.8. Arnold" \ "17 Feb 2005. Raised conc back to about 18 nM, for an " \ "nInit of precisely 1." \ "18 Feb. Doubled conc, to compensate for reduced ATP." \ "18 Feb. Doublec conc again, halved Vmax." call /kinetics/AC/CaM-bind-AC1/notes LOAD \ "Half-max at 20 nM CaM (Tang et al JBC 266:13 8595-8603 1991" \ "kb/kf = 20 nM = 12000 #/cell" \ "so kf = kb/12000 = kb * 8.333e-5" \ "" call /kinetics/AC/AC2*/notes LOAD \ "This version is activated by Gs and by a betagamma and phosphorylation." call /kinetics/AC/AC2*/kenz/notes LOAD \ "Reduced Km to match expt data for basal activation of AC2 by PKC." \ "Now k1 = 2.9e-6, k2 = 72, k3 = 18" \ "" \ "18 Feb: Raised Km to 300 based on BRENDA data." \ "Unlikely to make much difference, given the vast amount" \ "of ATP." call /kinetics/AC/AC2/notes LOAD \ "Starting at 0.015 uM." \ "17 Feb 2005: Raised slightly so as to have integer" \ "number of molecules." \ "18 Feb 2005: Doubled, to compensate for reduced ATP." call /kinetics/AC/dephosph-AC2/notes LOAD \ "Random rate." call /kinetics/AC/cAMP-PDE/notes LOAD \ "The levels of the PDE are not known at this time. However," \ "enough" \ "kinetic info and info about steady-state levels of cAMP" \ "etc are around" \ "to make it possible to estimate this." \ "18 Feb 2005: After some playing with initial conc, it is" \ "now back at 0.5 uM." call /kinetics/AC/cAMP-PDE/PDE/notes LOAD \ "Best rates are from Conti et al Biochem 34 7979-7987 1995." \ "Though these" \ "are for the Sertoli cell form, it looks like they carry" \ "nicely into" \ "alternatively spliced brain form. See Sette et al" \ "JBC 269:28 18271-18274" \ "Km ~2 uM, Vmax est ~ 10 umol/min/mg for pure form." \ "Brain protein is 93 kD but this was 67." \ "So k3 ~10, k2 ~40, k1 ~4.2e-6" call /kinetics/AC/cAMP-PDE*/notes LOAD \ "This form has about 2X activity as plain PDE. See Sette et al JBC 269:28" \ "18271-18274 1994." call /kinetics/AC/cAMP-PDE*/PDE*/notes LOAD \ "This form has about twice the activity of the unphosphorylated form. See" \ "Sette et al JBC 269:28 18271-18274 1994." \ "We'll ignore cGMP effects for now." call /kinetics/AC/dephosph-PDE/notes LOAD \ "The rates for this are poorly constrained. In adipocytes (probably a" \ "different PDE) the dephosphorylation is complete within 15 min, but" \ "there are no intermediate time points so it could be much faster. Identity" \ "of phosphatase etc is still unknown." call /kinetics/AC/PDE1/notes LOAD \ "CaM-Dependent PDE. Amount calculated from total rate in" \ "brain vs. specific rate. " call /kinetics/AC/PDE1/PDE1/notes LOAD \ "Rate is 1/6 of the CaM stim form. We'll just reduce" \ "all lf k1, k2, k3 so that the Vmax goes down 1/6." call /kinetics/AC/CaM.PDE1/notes LOAD \ "Activity up 6x following Ca-CaM binding." call /kinetics/AC/CaM.PDE1/CaM.PDE1/notes LOAD \ "Max activity ~10umol/min/mg in presence of lots of CaM." \ "Affinity is low, 40 uM." \ "k3 = 10, k2 = 40, k1 = (50/40) / 6e5." call /kinetics/AC/CaM_bind_PDE1/notes LOAD \ "For olf epi PDE1, affinity is 7 nM. Assume same for brain." \ "Reaction should be pretty fast. Assume kb = 5/sec." \ "Then kf = 5 / (0.007 * 6e5) = 1.2e-3" call /kinetics/AC/cAMP_in_dend/notes LOAD \ "Assume a 5 uM long segment of 1 uM^2 Xsection dendrite." \ "" call /kinetics/AC/cAMP_diffusion/notes LOAD \ "Represents diffusion, from a volume of 9e-20 to 5e-18." \ "Assuming neck dimensions of 0.1 x 0.1 microns, this" \ "works out to a diffusion const of about " \ "270 um^2/sec, which is pretty conservative. It is what" \ "cAMP does in frog cilia." \ "" call /kinetics/PKA/R2C2/notes LOAD \ "This is the R2C2 complex, consisting of 2 catalytic (C)" \ "subunits, and the R-dimer. See Taylor et al Ann Rev Biochem" \ "1990 59:971-1005 for a review." \ "The Doskeland and Ogreid review is better for numbers." \ "Amount of PKA is about .5 uM." call /kinetics/PKA/R2C2-cAMP/notes LOAD \ "CoInit was .0624" \ "" call /kinetics/PKA/cAMP-bind-site-B1/notes LOAD \ "Hasler et al FASEB J 6:2734-2741 1992 say Kd =1e-7M" \ "for type II, 5.6e-8 M for type I. Take mean" \ "which comes to 2e-13 #/cell" \ "Smith et al PNAS USA 78:3 1591-1595 1981 have better data." \ "First kf/kb=2.1e7/M = 3.5e-5 (#/cell)." \ "Ogreid and Doskeland Febs Lett 129:2 287-292 1981 have figs" \ "suggesting time course of complete assoc is < 1 min." call /kinetics/PKA/cAMP-bind-site-B2/notes LOAD \ "For now let us set this to the same Km (1e-7M) as" \ "site B. This gives kf/kb = .7e-7M * 1e6 / (6e5^2) : 1/(6e5^2)" \ "= 2e-13:2.77e-12" \ "Smith et al have better values. They say that this is" \ "cooperative, so the consts are now kf/kb =8.3e-4" call /kinetics/PKA/R2-cAMP4/notes LOAD \ "Starts at 0.15 for the test of fig 6 in Smith et al, but we aren't using" \ "that paper any more." call /kinetics/PKA/Release-C1/notes LOAD \ "This has to be fast, as the activation of PKA by cAMP" \ "is also fast." \ "kf was 10" \ "" call /kinetics/PKA/PKA-inhibitor/notes LOAD \ "About 25% of PKA C subunit is dissociated in resting cells without" \ "having any noticable activity." \ "Doskeland and Ogreid Int J biochem 13 pp1-19 suggest that this is" \ "because there is a corresponding amount of inhibitor protein." call /kinetics/PKA/inhib-PKA/notes LOAD \ "This has to be set to zero for matching the expts in vitro. In vivo" \ "we need to consider the inhibition though." \ "kf = 1e-5" \ "kb = 1" \ "" call /kinetics/PKC-active/phosph-AC2/notes LOAD \ "Phorbol esters have little effect on AC1 or on the Gs-stimulation of" \ "AC2. So in this model we are only dealing with the increase in" \ "basal activation of AC2 induced by PKC" \ "k1 = 1.66e-6" \ "k2 = 16" \ "k3 =4" \ "" call /kinetics/doqcsinfo/notes LOAD \ "This is the complete model of CaMKII bistability, model 3." \ "It exhibits bistability in CaMKII activation due to autophosphorylation" \ "at the PSD and local saturation of PP1." \ "This version of model 3 includes PKA regulatory input. This has" \ "little effect on the deterministic calculations, but the PKA " \ "pathway introduces a lot of noise which causes a difference in" \ "stochastic runs." complete_loading