//genesis // kkit Version 11 flat dumpfile // Saved on Mon Aug 7 15:52:39 2006 include kkit {argv 1} FASTDT = 2e-07 SIMDT = 4e-07 CONTROLDT = 1e-06 PLOTDT = 1e-08 MAXTIME = 0.1 TRANSIENT_TIME = 2 VARIABLE_DT_FLAG = 1 DEFAULT_VOL = 1.6667e-21 VERSION = 11.0 setfield /file/modpath value /home2/bhalla/scripts/modules kparms //genesis initdump -version 3 -ignoreorphans 1 simobjdump doqcsinfo filename accessname accesstype transcriber developer \ citation species tissue cellcompartment methodology sources \ model_implementation model_validation x y z simobjdump table input output alloced step_mode stepsize x y z simobjdump xtree path script namemode sizescale simobjdump xcoredraw xmin xmax ymin ymax simobjdump xtext editable simobjdump xgraph xmin xmax ymin ymax overlay simobjdump xplot pixflags script fg ysquish do_slope wy simobjdump group xtree_fg_req xtree_textfg_req plotfield expanded movealone \ link savename file version md5sum mod_save_flag x y z simobjdump geometry size dim shape outside xtree_fg_req xtree_textfg_req x y \ z simobjdump kpool DiffConst CoInit Co n nInit mwt nMin vol slave_enable \ geomname xtree_fg_req xtree_textfg_req x y z simobjdump kreac kf kb notes xtree_fg_req xtree_textfg_req x y z simobjdump kenz CoComplexInit CoComplex nComplexInit nComplex vol k1 k2 k3 \ keepconc usecomplex notes xtree_fg_req xtree_textfg_req link x y z simobjdump stim level1 width1 delay1 level2 width2 delay2 baselevel trig_time \ trig_mode notes xtree_fg_req xtree_textfg_req is_running x y z simobjdump xtab input output alloced step_mode stepsize notes editfunc \ xtree_fg_req xtree_textfg_req baselevel last_x last_y is_running x y z simobjdump kchan perm gmax Vm is_active use_nernst notes xtree_fg_req \ xtree_textfg_req x y z simobjdump transport input output alloced step_mode stepsize dt delay clock \ kf xtree_fg_req xtree_textfg_req x y z simobjdump proto x y z simobjdump text str simundump geometry /kinetics/geometry 0 1.6667e-21 3 sphere "" white black 3 \ 7 0 simundump kpool /kinetics/Im-nNOS 0 0 1 1 1 1 0 0 1 0 /kinetics/geometry blue \ black -4 6 0 simundump kreac /kinetics/Imidazole_release 0 57 0.07 "" white black 1 -2 0 simundump kpool /kinetics/Imidazole 0 0 0 0 0 0 0 0 1 0 /kinetics/geometry 46 \ black -4 -4 0 simundump kpool /kinetics/NOH-Arginine 0 0 6000 6000 6000 6000 0 0 1 0 \ /kinetics/geometry 8 black 6 6 0 simundump kreac /kinetics/NOH-Arginine_binding 0 25 67500 "" white black 1 4 \ 0 simundump kpool /kinetics/Im-nNOS-NOH-Arginine 0 0 0 0 0 0 0 0 1 0 \ /kinetics/geometry 25 black 1 1 0 simundump kpool /kinetics/nNOS-NOH-Arginine 0 0 0 0 0 0 0 0 1 0 \ /kinetics/geometry 0 black 5 -4 0 simundump doqcsinfo /kinetics/doqcsinfo 0 \ /home/harsha/Upload_model/NOH/NOHArginine.g NOHArginine pathway \ "Sharat J. Vayttaden and Prasoon Agarwal, NCBS" "Abu-Soud HM, Wang J, Rousseau DL, and Stuehr DJ" "" Human \ "Kidney cell expressing the rat brain nNOS" Cytosol \ "Quantitative match to experiments" \ "Abu-Soud HM et al. Biochemistry. 1999 Sep 21;38(38):12446-51. ( Peer-reviewed publication )" \ "Exact GENESIS implementation" "Approximates original data " 1 7 0 simundump xgraph /graphs/conc1 0 0 0.1 0 0.4 1 simundump xgraph /graphs/conc2 0 0 0.1 0 0.8 1 simundump xplot /graphs/conc1/Im-nNOS.Co 3 524288 \ "delete_plot.w ; edit_plot.D " blue 0 0 1 simundump xplot /graphs/conc2/Im-nNOS-NOH-Arginine.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 25 0 0 1 simundump xgraph /moregraphs/conc3 0 0 0.1 0 1 1 simundump xgraph /moregraphs/conc4 0 0 0.1 0 1 1 simundump xplot /moregraphs/conc3/NOH-Arginine.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 8 0 0 1 simundump xplot /moregraphs/conc3/Imidazole.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 46 0 0 1 simundump xplot /moregraphs/conc4/nNOS-NOH-Arginine.Co 3 524288 \ "delete_plot.w ; edit_plot.D " 0 0 0 1 simundump xcoredraw /edit/draw 0 -6 8 -6 9 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 \ "Model shows the substrate (NOH-Arginine) binding to nNOS " \ "in a two-step reversible fashion. First there is rapid " \ "binding equilibrium between Im-nNOS and NOH-Arginine to " \ "form an intermediate that contains bound imidazole and " \ "NOH-arginine. This is followed by a slower conformational " \ "change in the Im-enzyme-substrate complex that is associated " \ "with release of bound imidazole and generation of a " \ "modified enzyme-substrate complex which is detected " \ "due to spectral change." \ "" \ "Rates approximated based on data in Table 2." \ "The rates for first reaction are not exact since only " \ "Kd known and appropriate graphs do not exist for matching the " \ "kinetic profile." \ " " \ "Abu-Soud HM et al. Biochemistry. 1999 Sep 21;38(38):12446-51." addmsg /kinetics/NOH-Arginine_binding /kinetics/Im-nNOS REAC A B addmsg /kinetics/Im-nNOS-NOH-Arginine /kinetics/Imidazole_release SUBSTRATE n addmsg /kinetics/nNOS-NOH-Arginine /kinetics/Imidazole_release PRODUCT n addmsg /kinetics/Imidazole /kinetics/Imidazole_release PRODUCT n addmsg /kinetics/Imidazole_release /kinetics/Imidazole REAC B A addmsg /kinetics/NOH-Arginine_binding /kinetics/NOH-Arginine REAC A B addmsg /kinetics/NOH-Arginine /kinetics/NOH-Arginine_binding SUBSTRATE n addmsg /kinetics/Im-nNOS /kinetics/NOH-Arginine_binding SUBSTRATE n addmsg /kinetics/Im-nNOS-NOH-Arginine /kinetics/NOH-Arginine_binding PRODUCT n addmsg /kinetics/NOH-Arginine_binding /kinetics/Im-nNOS-NOH-Arginine REAC B A addmsg /kinetics/Imidazole_release /kinetics/Im-nNOS-NOH-Arginine REAC A B addmsg /kinetics/Imidazole_release /kinetics/nNOS-NOH-Arginine REAC B A addmsg /kinetics/Im-nNOS /graphs/conc1/Im-nNOS.Co PLOT Co *Im-nNOS.Co *blue addmsg /kinetics/Im-nNOS-NOH-Arginine /graphs/conc2/Im-nNOS-NOH-Arginine.Co PLOT Co *Im-nNOS-NOH-Arginine.Co *25 addmsg /kinetics/NOH-Arginine /moregraphs/conc3/NOH-Arginine.Co PLOT Co *NOH-Arginine.Co *8 addmsg /kinetics/Imidazole /moregraphs/conc3/Imidazole.Co PLOT Co *Imidazole.Co *46 addmsg /kinetics/nNOS-NOH-Arginine /moregraphs/conc4/nNOS-NOH-Arginine.Co PLOT Co *nNOS-NOH-Arginine.Co *0 enddump // End of dump call /kinetics/Im-nNOS/notes LOAD \ "Imidazole bound rat brain neuronal Nitric Oxide Synthase." \ "" \ "Abu-Soud HM et al. Biochemistry. 1999 Sep 21;38(38):12446-51." call /kinetics/Imidazole_release/notes LOAD \ "Release of Imidazole from complex of " \ "NOH-Arginine and Imidazole bound rat brain " \ "neuronal Nitric Oxide Synthase." \ "" \ "Abu-Soud HM et al. Biochemistry. 1999 Sep 21;38(38):12446-51." call /kinetics/Imidazole/notes LOAD \ "Imidazole released from the neuronal Nitric Oxide Synthase " \ "complexed to NOH-Arginine." \ "" \ "Abu-Soud HM et al. Biochemistry. 1999 Sep 21;38(38):12446-51." call /kinetics/NOH-Arginine/notes LOAD \ "N-hydroxyarginine, an alternative substrate for " \ "neuronal Nitric Oxide Synthase." \ "" \ "Abu-Soud HM et al. Biochemistry. 1999 Sep 21;38(38):12446-51." call /kinetics/NOH-Arginine_binding/notes LOAD \ "Binding of NOH-Arginine to Imidazole bound rat brain " \ "neuronal Nitric Oxide Synthase." \ "" \ "Only Kd is known, Kf and Kb need to be approximated" \ "accordingly to match kinetic profiles. Due to lack of " \ "appropriate graphs the choice of Kf and Kb here is " \ "arbitrary and matches only the Kd." \ "" \ "Kd = 2.7mM = 2700uM" \ "" \ "Abu-Soud HM et al. Biochemistry. 1999 Sep 21;38(38):12446-51." call /kinetics/Im-nNOS-NOH-Arginine/notes LOAD \ "An intermediate formed due to rapid binding of NOH-Arginine " \ "to Imidazole bound neuronal Nitric Oxide Synthase." \ "" \ "Abu-Soud HM et al. Biochemistry. 1999 Sep 21;38(38):12446-51." call /kinetics/nNOS-NOH-Arginine/notes LOAD \ "NOH-Arginine bound to neuronal Nitric Oxide Synthase." \ "" \ "Abu-Soud HM et al. Biochemistry. 1999 Sep 21;38(38):12446-51." call /kinetics/doqcsinfo/notes LOAD \ "This model is taken from the Abu-Soud HM et al. Biochemistry. 1999 Sep 21;38(38):12446-51." \ "This model shows kinetic binding of NOHArginine to neuronal nitric oxide synthase." \ " " \ "Model shows the substrate (NOH-Arginine) binding to nNOS " \ "in a two-step reversible fashion. First there is rapid " \ "binding equilibrium between Im-nNOS and NOH-Arginine to " \ "form an intermediate that contains bound imidazole and " \ "NOH-arginine. This is followed by a slower conformational" \ "change in the Im-enzyme-substrate complex that is associated " \ "with release of bound imidazole and generation of a " \ "modified enzyme-substrate complex which is detected " \ "due to spectral change." \ "" \ "Rates approximated based on data in Table 2." \ "The rates for first reaction are not exact since only " \ "Kd known and appropriate graphs do not exist for matching the " \ "kinetic profile." complete_loading