// DOQCS : http://doqcs.ncbs.res.in/ // Accession Name = MAPK_Asthagiri_enz_fb // Accession Number = 46 // Transcriber = Pradeep Kumar S, NCBS // Developer = Anand R. Asthagiri and Douglas A. Lauffenburger // Species = Chinese hamster (Cricetulus griseus); mammalian // Tissue = Ovary - CHO cell line // Cell Compartment = Surface + cytosol // Notes = This is a complex model to examine mechanisms that govern MAPK pathway dynamics in Chinese hamster ovary (CHO) cell lines, particularly the role of enzyme targeted negative feedback mechanism in generating downstream signal adaptation. This model simulates the results as per the simulation conditions specified for figure 7B of the paper by Asthagiri AR and Lauffenburger DA. Biotechnol Prog. (2001) 17(2):227-39.
However, there is some discrepancy with the outputs shown in Figure 7B. //genesis // kkit Version 11 flat dumpfile // Saved on Fri Dec 9 11:07:18 2005 include kkit {argv 1} FASTDT = 0.0001 SIMDT = 0.01 CONTROLDT = 5 PLOTDT = 1 MAXTIME = 5000 TRANSIENT_TIME = 2 VARIABLE_DT_FLAG = 0 DEFAULT_VOL = 3.9e-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 simundump geometry /kinetics/geometry 0 3.9e-16 3 sphere "" white black 17 3 \ 0 simundump kpool /kinetics/L 0 0 0.03 0.03 7020 7020 0 0 2.34e+05 4 \ /kinetics/geometry blue black -4 2 0 simundump kpool /kinetics/R 0 0 0.42735 0.42735 1e+05 1e+05 0 0 2.34e+05 0 \ /kinetics/geometry blue black -4 0 0 simundump kreac /kinetics/L-bind-R 0 7.1197e-07 0.005 "" white black -2 1 0 simundump kpool /kinetics/C 0 0 0 0 0 0 0 0 2.34e+05 0 /kinetics/geometry \ blue black 0 0 0 simundump kreac /kinetics/C-dimer 0 4.2735e-06 1 "" white black 2 1 0 simundump kpool /kinetics/C* 0 0 0 0 0 0 0 0 2.34e+05 0 /kinetics/geometry \ blue black 8 0 0 simundump kpool /kinetics/C2 0 0 0 0 0 0 0 0 2.34e+05 0 /kinetics/geometry \ blue black 4 0 0 simundump kreac /kinetics/C2-phos 0 0.833 0.0833 "" white black 6 1 0 simundump kpool /kinetics/A1 0 0 0.042735 0.042735 10000 10000 0 0 2.34e+05 0 \ /kinetics/geometry blue black 8 2 0 simundump kreac /kinetics/C*-bind-A1 0 2.1368e-05 0.50001 "" white black 10 1 \ 0 simundump kpool /kinetics/A2 0 0 0.042735 0.042735 10000 10000 0 0 2.34e+05 0 \ /kinetics/geometry blue black 8 3 0 simundump kreac /kinetics/C*A1-bind-A2 0 2.1368e-05 0.50001 "" white black 14 \ 1 0 simundump kpool /kinetics/C*A1 0 0 0 0 0 0 0 0 2.34e+05 0 /kinetics/geometry \ blue black 12 0 0 simundump kreac /kinetics/A1-bind-A2 0 2.1368e-05 0.50001 "" white black -4 3 \ 0 simundump kpool /kinetics/A1A2 0 0 0 0 0 0 0 0 2.34e+05 0 /kinetics/geometry \ blue black -9 1 0 simundump kreac /kinetics/C*-bind-A1A2 0 2.1368e-05 0.50001 "" white black -4 \ -1 0 simundump kpool /kinetics/E0* 0 0 0 0 0 0 0 0 2.34e+05 0 /kinetics/geometry 0 \ black 17 -1 0 simundump kenz /kinetics/E0*/E1_activ 0 0 0 0 0 2.34e+05 4.2735e-05 0.5 0.1 0 \ 0 "" red 0 "" 17 -2 0 simundump kpool /kinetics/E1 0 0 0.042735 0.042735 10000 10000 0 0 2.34e+05 0 \ /kinetics/geometry blue black 19 -3 0 simundump kpool /kinetics/E1* 0 0 0 0 0 0 0 0 2.34e+05 0 /kinetics/geometry \ 29 black 12 -3 0 simundump kenz /kinetics/E1*/E2_activ 0 0 0 0 0 2.34e+05 4.2735e-05 0.5 0.1 0 \ 0 "" red 29 "" 12 -4 0 simundump kpool /kinetics/P1 0 0 0.021368 0.021368 5000 5000 0 0 2.34e+05 0 \ /kinetics/geometry blue black 17 -5 0 simundump kenz /kinetics/P1/E1*_deactiv 0 0 0 0 0 2.34e+05 4.2735e-05 0.5 0.1 \ 0 0 "" red blue "" 17 -4 0 simundump kpool /kinetics/E2 0 0 0.042735 0.042735 10000 10000 0 0 2.34e+05 0 \ /kinetics/geometry blue black 15 -5 0 simundump kpool /kinetics/E2* 0 0 0 0 0 0 0 0 2.34e+05 0 /kinetics/geometry \ 42 black 7 -5 0 simundump kenz /kinetics/E2*/E3_activ 0 0 0 0 0 2.34e+05 4.2735e-05 0.5 0.1 0 \ 0 "" red 42 "" 7 -6 0 simundump kpool /kinetics/P2 0 0 0.021368 0.021368 5000 5000 0 0 2.34e+05 0 \ /kinetics/geometry blue black 12 -7 0 simundump kenz /kinetics/P2/E2*_deactiv 0 0 0 0 0 2.34e+05 4.2735e-05 0.5 0.1 \ 0 0 "" red blue "" 12 -6 0 simundump kpool /kinetics/E3 0 0 0.042735 0.042735 10000 10000 0 0 2.34e+05 0 \ /kinetics/geometry blue black 10 -7 0 simundump kpool /kinetics/E3* 0 0 0 0 0 0 0 0 2.34e+05 0 /kinetics/geometry \ 48 black 2 -7 0 simundump kenz /kinetics/E3*/E4_activ 0 0 0 0 0 2.34e+05 4.2735e-05 0.5 0.1 0 \ 0 "" red 48 "" 2 -8 0 simundump kpool /kinetics/P3 0 0 0.021368 0.021368 5000 5000 0 0 2.34e+05 0 \ /kinetics/geometry blue black 7 -9 0 simundump kenz /kinetics/P3/E3*_deactiv 0 0 0 0 0 2.34e+05 4.2735e-05 0.5 0.1 \ 0 0 "" red blue "" 7 -8 0 simundump kpool /kinetics/E4 0 0 0.042735 0.042735 10000 10000 0 0 2.34e+05 0 \ /kinetics/geometry blue black 5 -9 0 simundump kpool /kinetics/E4* 0 0 0 0 0 0 0 0 2.34e+05 0 /kinetics/geometry \ 50 black -3 -9 0 simundump kenz /kinetics/E4*/E5_activ 0 0 0 0 0 2.34e+05 4.2735e-05 0.5 0.1 0 \ 0 "" red 50 "" -3 -10 0 simundump kenz /kinetics/E4*/E4*_enz_targeted_fb 0 0 0 0 0 2.34e+05 \ 4.2735e-05 0.5 0.1 0 0 "" red 50 "" -5 -8 0 simundump kpool /kinetics/P4 0 0 0.021368 0.021368 5000 5000 0 0 2.34e+05 0 \ /kinetics/geometry blue black 2 -11 0 simundump kenz /kinetics/P4/E4*_deactiv 0 0 0 0 0 2.34e+05 4.2735e-05 0.5 0.1 \ 0 0 "" red blue "" 2 -10 0 simundump kpool /kinetics/E5 0 0 0.042735 0.042735 10000 10000 0 0 2.34e+05 0 \ /kinetics/geometry blue black 0 -11 0 simundump kpool /kinetics/P5 0 0 0.021368 0.021368 5000 5000 0 0 2.34e+05 0 \ /kinetics/geometry blue black -3 -13 0 simundump kenz /kinetics/P5/E5*_deactiv 0 0 0 0 0 2.34e+05 4.2735e-05 0.5 0.1 \ 0 0 "" red blue "" -3 -12 0 simundump kpool /kinetics/E5* 0 0 0 0 0 0 0 0 2.34e+05 0 /kinetics/geometry \ 60 black -8 -11 0 simundump kpool /kinetics/E2- 0 0 0 0 0 0 0 0 2.34e+05 0 /kinetics/geometry \ blue black -6 -5 0 simundump doqcsinfo /kinetics/doqcsinfo 0 db46.g MAPK_Asthagiri_enz_fb \ pathway " Pradeep Kumar S, NCBS" \ " Anand R. Asthagiri and Douglas A. Lauffenburger" "citation here" \ " Chinese hamster (Cricetulus griseus); mammalian" " Ovary - CHO cell line" \ "Surface + Cytosol" Qualitative \ "Asthagiri AR and Lauffenburger DA. Biotechnol Prog. (2001) 17(2):227-39. ( peer-reviewed publication )." \ "Approximate implementation" "Approximates original data " 17 4 0 simundump xgraph /graphs/conc1 0 0 5000 0 0.014135 0 simundump xgraph /graphs/conc2 0 0 5000 0 1 0 simundump xplot /graphs/conc1/E1*.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 29 0 0 1 simundump xplot /graphs/conc1/E2*.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 42 0 0 1 simundump xplot /graphs/conc1/E3*.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 48 0 0 1 simundump xplot /graphs/conc1/E4*.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 50 0 0 1 simundump xplot /graphs/conc1/E5*.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 60 0 0 1 simundump xplot /graphs/conc1/E0*.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 0 0 0 1 simundump xgraph /moregraphs/conc3 0 0 5000 0 1 0 simundump xgraph /moregraphs/conc4 0 0 5000 0 1 0 simundump xcoredraw /edit/draw 0 -11 21 -15 5 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 \ "This is GENESIS model based on : " \ "A computational study of feedback effects on signal dynamics in" \ "a mitogen-activated kinase(MAPK) pathway model by" \ "Anand R. Asthagiri* and Douglas A. Lauffenburger" \ "Biotechnol. Prog. 2001, 17, 227-239." \ "" \ "Note: " \ "1. Volume of the pools were set to 3.9e-16." \ "2. L was buffered at the CoInit = 0.03uM." \ "3. All the parameters were obtained from above mentioned literature" \ "" \ "Simulation:" \ "This modle simulates figure 7b of paper which indicates mechanism of adaptation" \ "in the presence of enzyme targeted feedback control." \ " Enzyme targeted feedback enables adaptation of the target signal e2*" \ " and signals downstream of the target, but not those signals upstream of the target e0* and e1*. " \ "" \ "Note:" \ "Results in figure 4 of paper are total no of active enzyme (ei*)" \ "normalized using total enzyme at each level E^Ti. But actual graphs" \ "ploted in genesis is equivalent concentration uM to that of no of enzymes" \ "actual quantity of enzyme in no. of active enzyme can be obtained" \ "by going to each stage of the enzyme cascade and getting n for each of" \ "active enzyme (ei*) and then dividing that by the total enzyme (E^Ti) at" \ "each stage. " \ "summary : " \ "ei* = (total no. of active enzyme/total no. of enzyme at that level" \ "" \ "Example: " \ "Let kpool e1's n=1666.6 got after running simulation for 1000sec" \ " & nInit = 10^4 no.cells then normalized value will" \ " be 0.1666." \ "" \ "" addmsg /kinetics/L-bind-R /kinetics/L REAC A B addmsg /kinetics/L-bind-R /kinetics/R REAC A B addmsg /kinetics/L /kinetics/L-bind-R SUBSTRATE n addmsg /kinetics/R /kinetics/L-bind-R SUBSTRATE n addmsg /kinetics/C /kinetics/L-bind-R PRODUCT n addmsg /kinetics/L-bind-R /kinetics/C REAC B A addmsg /kinetics/C-dimer /kinetics/C REAC A B addmsg /kinetics/C-dimer /kinetics/C REAC A B addmsg /kinetics/C /kinetics/C-dimer SUBSTRATE n addmsg /kinetics/C /kinetics/C-dimer SUBSTRATE n addmsg /kinetics/C2 /kinetics/C-dimer PRODUCT n addmsg /kinetics/C2-phos /kinetics/C* REAC B A addmsg /kinetics/C*-bind-A1 /kinetics/C* REAC A B addmsg /kinetics/C*-bind-A1A2 /kinetics/C* REAC A B addmsg /kinetics/C-dimer /kinetics/C2 REAC B A addmsg /kinetics/C2-phos /kinetics/C2 REAC A B addmsg /kinetics/C2 /kinetics/C2-phos SUBSTRATE n addmsg /kinetics/C* /kinetics/C2-phos PRODUCT n addmsg /kinetics/C*-bind-A1 /kinetics/A1 REAC A B addmsg /kinetics/A1-bind-A2 /kinetics/A1 REAC A B addmsg /kinetics/C* /kinetics/C*-bind-A1 SUBSTRATE n addmsg /kinetics/A1 /kinetics/C*-bind-A1 SUBSTRATE n addmsg /kinetics/C*A1 /kinetics/C*-bind-A1 PRODUCT n addmsg /kinetics/C*A1-bind-A2 /kinetics/A2 REAC A B addmsg /kinetics/A1-bind-A2 /kinetics/A2 REAC A B addmsg /kinetics/C*A1 /kinetics/C*A1-bind-A2 SUBSTRATE n addmsg /kinetics/A2 /kinetics/C*A1-bind-A2 SUBSTRATE n addmsg /kinetics/E0* /kinetics/C*A1-bind-A2 PRODUCT n addmsg /kinetics/C*-bind-A1 /kinetics/C*A1 REAC B A addmsg /kinetics/C*A1-bind-A2 /kinetics/C*A1 REAC A B addmsg /kinetics/A2 /kinetics/A1-bind-A2 SUBSTRATE n addmsg /kinetics/A1 /kinetics/A1-bind-A2 SUBSTRATE n addmsg /kinetics/A1A2 /kinetics/A1-bind-A2 PRODUCT n addmsg /kinetics/A1-bind-A2 /kinetics/A1A2 REAC B A addmsg /kinetics/C*-bind-A1A2 /kinetics/A1A2 REAC A B addmsg /kinetics/A1A2 /kinetics/C*-bind-A1A2 SUBSTRATE n addmsg /kinetics/E0* /kinetics/C*-bind-A1A2 PRODUCT n addmsg /kinetics/C* /kinetics/C*-bind-A1A2 SUBSTRATE n addmsg /kinetics/C*A1-bind-A2 /kinetics/E0* REAC B A addmsg /kinetics/C*-bind-A1A2 /kinetics/E0* REAC B A addmsg /kinetics/E0*/E1_activ /kinetics/E0* REAC eA B addmsg /kinetics/E0* /kinetics/E0*/E1_activ ENZYME n addmsg /kinetics/E1 /kinetics/E0*/E1_activ SUBSTRATE n addmsg /kinetics/E0*/E1_activ /kinetics/E1 REAC sA B addmsg /kinetics/P1/E1*_deactiv /kinetics/E1 MM_PRD pA addmsg /kinetics/E0*/E1_activ /kinetics/E1* MM_PRD pA addmsg /kinetics/P1/E1*_deactiv /kinetics/E1* REAC sA B addmsg /kinetics/E1*/E2_activ /kinetics/E1* REAC eA B addmsg /kinetics/E1* /kinetics/E1*/E2_activ ENZYME n addmsg /kinetics/E2 /kinetics/E1*/E2_activ SUBSTRATE n addmsg /kinetics/P1/E1*_deactiv /kinetics/P1 REAC eA B addmsg /kinetics/P1 /kinetics/P1/E1*_deactiv ENZYME n addmsg /kinetics/E1* /kinetics/P1/E1*_deactiv SUBSTRATE n addmsg /kinetics/E1*/E2_activ /kinetics/E2 REAC sA B addmsg /kinetics/P2/E2*_deactiv /kinetics/E2 MM_PRD pA addmsg /kinetics/E1*/E2_activ /kinetics/E2* MM_PRD pA addmsg /kinetics/P2/E2*_deactiv /kinetics/E2* REAC sA B addmsg /kinetics/E2*/E3_activ /kinetics/E2* REAC eA B addmsg /kinetics/E4*/E4*_enz_targeted_fb /kinetics/E2* REAC sA B addmsg /kinetics/E2* /kinetics/E2*/E3_activ ENZYME n addmsg /kinetics/E3 /kinetics/E2*/E3_activ SUBSTRATE n addmsg /kinetics/P2/E2*_deactiv /kinetics/P2 REAC eA B addmsg /kinetics/P2 /kinetics/P2/E2*_deactiv ENZYME n addmsg /kinetics/E2* /kinetics/P2/E2*_deactiv SUBSTRATE n addmsg /kinetics/E2*/E3_activ /kinetics/E3 REAC sA B addmsg /kinetics/P3/E3*_deactiv /kinetics/E3 MM_PRD pA addmsg /kinetics/E2*/E3_activ /kinetics/E3* MM_PRD pA addmsg /kinetics/P3/E3*_deactiv /kinetics/E3* REAC sA B addmsg /kinetics/E3*/E4_activ /kinetics/E3* REAC eA B addmsg /kinetics/E3* /kinetics/E3*/E4_activ ENZYME n addmsg /kinetics/E4 /kinetics/E3*/E4_activ SUBSTRATE n addmsg /kinetics/P3/E3*_deactiv /kinetics/P3 REAC eA B addmsg /kinetics/P3 /kinetics/P3/E3*_deactiv ENZYME n addmsg /kinetics/E3* /kinetics/P3/E3*_deactiv SUBSTRATE n addmsg /kinetics/E3*/E4_activ /kinetics/E4 REAC sA B addmsg /kinetics/P4/E4*_deactiv /kinetics/E4 MM_PRD pA addmsg /kinetics/E3*/E4_activ /kinetics/E4* MM_PRD pA addmsg /kinetics/P4/E4*_deactiv /kinetics/E4* REAC sA B addmsg /kinetics/E4*/E5_activ /kinetics/E4* REAC eA B addmsg /kinetics/E4*/E4*_enz_targeted_fb /kinetics/E4* REAC eA B addmsg /kinetics/E4* /kinetics/E4*/E5_activ ENZYME n addmsg /kinetics/E5 /kinetics/E4*/E5_activ SUBSTRATE n addmsg /kinetics/E4* /kinetics/E4*/E4*_enz_targeted_fb ENZYME n addmsg /kinetics/E2* /kinetics/E4*/E4*_enz_targeted_fb SUBSTRATE n addmsg /kinetics/P4/E4*_deactiv /kinetics/P4 REAC eA B addmsg /kinetics/P4 /kinetics/P4/E4*_deactiv ENZYME n addmsg /kinetics/E4* /kinetics/P4/E4*_deactiv SUBSTRATE n addmsg /kinetics/E4*/E5_activ /kinetics/E5 REAC sA B addmsg /kinetics/P5/E5*_deactiv /kinetics/E5 MM_PRD pA addmsg /kinetics/P5/E5*_deactiv /kinetics/P5 REAC eA B addmsg /kinetics/P5 /kinetics/P5/E5*_deactiv ENZYME n addmsg /kinetics/E5* /kinetics/P5/E5*_deactiv SUBSTRATE n addmsg /kinetics/E4*/E5_activ /kinetics/E5* MM_PRD pA addmsg /kinetics/P5/E5*_deactiv /kinetics/E5* REAC sA B addmsg /kinetics/E4*/E4*_enz_targeted_fb /kinetics/E2- MM_PRD pA addmsg /kinetics/E1* /graphs/conc1/E1*.Co PLOT Co *E1*.Co *29 addmsg /kinetics/E2* /graphs/conc1/E2*.Co PLOT Co *E2*.Co *42 addmsg /kinetics/E3* /graphs/conc1/E3*.Co PLOT Co *E3*.Co *48 addmsg /kinetics/E4* /graphs/conc1/E4*.Co PLOT Co *E4*.Co *50 addmsg /kinetics/E5* /graphs/conc1/E5*.Co PLOT Co *E5*.Co *60 addmsg /kinetics/E0* /graphs/conc1/E0*.Co PLOT Co *E0*.Co *0 enddump // End of dump call /kinetics/L/notes LOAD \ "L CoInit = buffered at 0.03 uM" \ "from" \ "Asthagiri, A.R and Lauffenburger, D.A " \ "Biotechnol. Prog. 2001, 17, 227-239." \ "" \ "" call /kinetics/R/notes LOAD \ "R nInit = 10^5 no./cell" \ "from" \ "Asthagiri, A.R and Lauffenburger, D.A" \ "Biotechnol. Prog. 2001. 17,227-239. " call /kinetics/L-bind-R/notes LOAD \ "Kf = 10^7/M-1 min-1 and Kr is 0.3 min-1" \ "from" \ "Asthagiri, A.R and Lauffenburger, D.A" \ "Biotechnol. Prog. 2001, 17, 227-239." call /kinetics/C/notes LOAD \ "Ligand bound receptor" \ "from" \ "Asthagiri and Lauffenburger 2001" call /kinetics/C-dimer/notes LOAD \ "Kc is 6*10^7 M-1 min-1 and Ku is 60 min-1" \ "from" \ "Asthagiri, A.R and Lauffenburger, D.A " \ "Biotechnol. Prog. 2001, 17, 227-239." call /kinetics/C*/notes LOAD \ "Activated form of receptor" \ "from" \ "Asthagiri and Lauffenburger 2001" call /kinetics/C2/notes LOAD \ "Dimer formed by receptor binding" \ "from" \ "Asthagiri and Lauffenburger 2001" call /kinetics/C2-phos/notes LOAD \ "Kc+ is 50min-1 and Kc- is 5min-1" \ "from" \ "Asthagiri and Lauffenburger 2001." call /kinetics/A1/notes LOAD \ "First adaptor protein. Tot.no. 10^4 no./cell" \ "from" \ "Asthagiri and Lauffenburger 2001" call /kinetics/C*-bind-A1/notes LOAD \ "Kf1 is 3*10^8 M-1 min-1 and Kr1 is 0.5/sec" \ "from" \ "Asthagiri and Lauffenburger 2001" call /kinetics/A2/notes LOAD \ "Second adaptor protein. Tot.no. 10^4 no./cell" \ "from" \ "Asthagiri and Lauffenburger 2001" call /kinetics/C*A1-bind-A2/notes LOAD \ "kf2 and kr2 are 3*10^8 M-1 min-1 and 0.5/sec" \ "from " \ "Asthagiri and Lauffenburger , 20001." call /kinetics/C*A1/notes LOAD \ "Adaptor protein bound activated receptor" \ "from" \ "Asthagiri and Lauffenburger 2001" call /kinetics/A1-bind-A2/notes LOAD \ "Kc12 and Kd12 are 3*10^8 M-1 min-1 and 0.5/sec" \ "from" \ "Asthagiri and Lauffenburger 2001." call /kinetics/A1A2/notes LOAD \ "Adaptor protein heterodimer" \ "from" \ "Asthagiri and Lauffenburger 2001." call /kinetics/C*-bind-A1A2/notes LOAD \ "Kf12 and Kr12 are 3*10^8 M-1 min-1 and 0.5/sec" \ "from" \ "Asthagiri and Lauffenburger 2001." call /kinetics/E0*/notes LOAD \ "Active form of enzyme" \ "from" \ "Asthagiri and Lauffenburger, 2001" \ "" call /kinetics/E0*/E1_activ/notes LOAD \ "k1+ =6*10^8 M-1 min-1, k1- =30 min-1, kcat,1 =6 min-1 and km caluculated to 0.06" \ "from" \ "Asthagiri and Lauffenburger 2001." call /kinetics/E1/notes LOAD \ "E1^T = 10^4 no./cell" \ "from " \ "Asthagiri and Lauffenburger 2001" call /kinetics/E1*/notes LOAD \ "Active form of enzyme" \ "from" \ "Asthagiri and Lauffenburger, 2001" \ "" call /kinetics/E1*/E2_activ/notes LOAD \ "k2+ =6*10^8 M-1 min-1, k2- =30 min-1, kcat,2 =6 min-1" \ "from" \ "Asthagire and Lauffenburger 2001" call /kinetics/P1/notes LOAD \ "Deactivating enzyme, P1^T = 5000 no./cell" \ "from" \ "Asthagiri and Lauffenburger, 2001" call /kinetics/P1/E1*_deactiv/notes LOAD \ "kp1+ =6*10^8 M-1 min-1, kp1- =30 min-1, kpcat,1 =6 min-1" \ "form" \ "Asthagiri and Lauffenburger 2001." call /kinetics/E2/notes LOAD \ "E2^T =10^4 no./cell" \ "from" \ "Asthagiri and Lauffenburger 2001." call /kinetics/E2*/notes LOAD \ "Active form of enzyme" \ "from" \ "Asthagiri and Lauffenburger, 2001" \ "" call /kinetics/E2*/E3_activ/notes LOAD \ "k3+ =6*10^8 M-1 min-1, k3- =30 min-1, kcat,3 =6 min-1" \ "from" \ "Asthagiri and Lauffenburger 2001." call /kinetics/P2/notes LOAD \ "Deactivating enzyme P2^T = 5000 no./cell." \ "from" \ "Asthagiri and Lauffenburger, 2001." call /kinetics/P2/E2*_deactiv/notes LOAD \ "kp2+ =6*10^8 M-1 min-1, kp2- = 30 min-1, kpcat,2 = 6 min-1" \ "from" \ "Asthagiri and Lauffenburger 2001." call /kinetics/E3/notes LOAD \ "E3^T =10^4 no./cell" \ "from" \ "Asthagiri and Lauffenburger 2001." call /kinetics/E3*/notes LOAD \ "Active form of enzyme" \ "from" \ "Asthagiri and Lauffenburger, 2001" \ "" call /kinetics/E3*/E4_activ/notes LOAD \ "k4+ = 6*10^8 M-1 min-1, k4- =30 min-1, kcat,4 =6 min-1" \ "from" \ "Asthagiri and Lauffenburger 2001." call /kinetics/P3/notes LOAD \ "Deactivating enzyme P3^T = 5000 no./cell" \ "from" \ "Asthagiri and Lauffenburger, 2001" call /kinetics/P3/E3*_deactiv/notes LOAD \ "kp3+ =6*10^8 M-1 min-1, kp3- =30 min-1, kpcat,3 =6 min-1" \ "from" \ "Asthagiri and Lauffenburger 2001." call /kinetics/E4/notes LOAD \ "E4^T =10^4 no./cell" \ "from" \ "Asthagiri and Lauffenburger 2001" call /kinetics/E4*/notes LOAD \ "Active form of enzyme" \ "from" \ "Asthagiri and Lauffenburger, 2001" \ "" call /kinetics/E4*/E5_activ/notes LOAD \ "k5+ =6*10^8 M-1 min-1, k5- =30 min-1, kcat,5 =6 min-1" \ "from" \ "Asthagiri and Lauffenburger 2001." call /kinetics/E4*/E4*_enz_targeted_fb/notes LOAD \ "Implementation of enzyme feedback induces adaptation of e2*" \ "and signals downstream of the target signal, but not those" \ "signals upstream of the target e0* and e1*." \ "" \ "k5+ =6*10^8 M-1 min-1, k5- =30 min-1, kcat,5 =6 min-1" \ "from" \ "Asthagiri and Lauffenburger 2001." \ "" call /kinetics/P4/notes LOAD \ "Deactivating enzyme P4^T = 5000 no./cell." \ "from " \ "Asthagiri and Lauffenburger, 2001" call /kinetics/P4/E4*_deactiv/notes LOAD \ "kp4+ = 6*10^8 M-1 min-1, kp4- =30 min-1, kpcat,4 =6 min-1" \ "from" \ "Asthagiri and Lauffenburger 2001." call /kinetics/E5/notes LOAD \ "E5^T = 10^4 no./cell" \ "from" \ "Asthagiri and Lauffenburger 2001" call /kinetics/P5/notes LOAD \ "Deactivating enzyme P5^T = 5000 no./cell" \ "from" \ "Asthagiri and Lauffenburger, 2001." call /kinetics/P5/E5*_deactiv/notes LOAD \ "kp5+ = 6*10^8 M-1 min-1, kp5- = 30 min-1, kpcat,5 = 6 min-1" \ "from" \ "Asthagiri and Lauffenburger 2001." call /kinetics/E5*/notes LOAD \ "Active form of enzyme" \ "from" \ "Asthagiri and Lauffenburger, 2001" \ "" call /kinetics/E2-/notes LOAD \ "Nonfunctional second enzyme of enzyme cascade E2-" \ "from" \ "Asthagiri and Lauffnburger, 2001" call /kinetics/doqcsinfo/notes LOAD \ "This is a complex model to examine mechanisms that govern MAPK pathway dynamics in Chinese hamster ovary (CHO) cell lines, particularly the role of enzyme targeted negative feedback mechanism in generating downstream signal adaptation. This model simulates the results as per the simulation conditions specified for figure 7B of the paper by Asthagiri AR and Lauffenburger DA. Biotechnol Prog. (2001) 17(2):227-39.
However, there is some discrepancy with the outputs shown in Figure 7B." complete_loading