//genesis
// kkit Version 8 flat dumpfile
 
// Saved on Mon Jan 28 01:16:45 2002
 
include kkit {argv 1}
 
FASTDT = 5e-05
SIMDT = 0.005
CONTROLDT = 5
PLOTDT = 1
MAXTIME = 2100
TRANSIENT_TIME = 2
VARIABLE_DT_FLAG = 1
DEFAULT_VOL = 1e-18
VERSION = 8.0
setfield /file/modpath value /home2/bhalla/scripts/modules
kparms
 
//genesis

initdump -version 3 -ignoreorphans 1
simobjdump table input output alloced step_mode stepsize x y z
simobjdump xtree path script namemode sizescale
simobjdump xcoredraw xmin xmax ymin ymax
simobjdump xtext editable
simobjdump xgraph xmin xmax ymin ymax overlay
simobjdump xplot pixflags script fg ysquish do_slope wy
simobjdump group xtree_fg_req xtree_textfg_req plotfield expanded movealone \
  link savename file version md5sum mod_save_flag x y z
simobjdump kpool CoTotal CoInit Co n nInit nTotal nMin vol slave_enable notes \
  xtree_fg_req xtree_textfg_req x y z
simobjdump kreac kf kb notes xtree_fg_req xtree_textfg_req x y z
simobjdump kenz CoComplexInit CoComplex nComplexInit nComplex vol k1 k2 k3 \
  keepconc usecomplex notes xtree_fg_req xtree_textfg_req link x y z
simobjdump stim level1 width1 delay1 level2 width2 delay2 baselevel trig_time \
  trig_mode notes xtree_fg_req xtree_textfg_req is_running x y z
simobjdump xtab input output alloced step_mode stepsize notes editfunc \
  xtree_fg_req xtree_textfg_req baselevel last_x last_y is_running x y z
simobjdump kchan perm gmax Vm is_active use_nernst notes xtree_fg_req \
  xtree_textfg_req x y z
simobjdump proto x y z
simobjdump linkinfo xtree_fg_req xtree_textfg_req uplink downlink x y z
simobjdump uplink xtree_fg_req xtree_textfg_req x y z
simobjdump downlink xtree_fg_req xtree_textfg_req x y z
simobjdump mirror notes xtree_fg_req x y z
simundump group /kinetics/LacZ 0 23 black x 0 0 "" LacZ \
  /home2/bhalla/scripts/modules/LacZ_0.g 0 0 0 -7 3 0
simundump kpool /kinetics/LacZ/Ribosome 0 583.35 0.58335 0.58335 350 350 \
  3.5e+05 0 599.98 4 "" 49 23 -7 -2 0
simundump kpool /kinetics/LacZ/Protein 0 0 0 0 0 0 0 0 599.98 0 "" 7 23 -7 -4 \
  0
simundump kpool /kinetics/LacZ/AAs 0 0 0 0 0 0 0 0 599.98 4 "" 1 23 -7 -6 0
simundump kreac /kinetics/LacZ/Ribosome_binding 0 0.16666 2.25 "" white 23 -5 \
  -1 0
simundump kreac /kinetics/LacZ/Prot_elongation 0 0.015 0 "" white 23 -5 -3 0
simundump kreac /kinetics/LacZ/Prot_degradation 0 6.42e-05 0 "" white 23 -5 \
  -5 0
simundump kpool /kinetics/LacZ/RNAP 0 58.335 0.058335 0.058335 35 35 35000 0 \
  599.98 4 "" 61 23 -3 2 0
simundump kpool /kinetics/LacZ/RBS 0 0 0 0 0 0 0 0 599.98 0 "" 2 23 -3 0 0
simundump kpool /kinetics/LacZ/RibRBS 0 0 0 0 0 0 0 0 599.98 0 "" 6 23 -3 -2 \
  0
simundump kpool /kinetics/LacZ/elRIB 0 0 0 0 0 0 0 0 599.98 0 "" 57 23 -3 -4 \
  0
simundump kreac /kinetics/LacZ/RNAPol_binding 0 0.16666 10 "" white 23 -1 3 0
simundump kreac /kinetics/LacZ/RNASynthesis 0 1 0 "" white 23 -1 1 0
simundump kreac /kinetics/LacZ/RBS_degradation 0 0.3 0 "" white 23 -1 -1 0
simundump kreac /kinetics/LacZ/Clearance 0 0.5 0 "" white 23 -1 -3 0
simundump kpool /kinetics/LacZ/P_RNAP 0 0 0 0 0 0 0 0 599.98 0 "" 30 23 1 4 0
simundump kpool /kinetics/LacZ/P 0 1.6667 0.0016667 0.0016667 1 1 1000 0 \
  599.98 0 "" 29 23 1 2 0
simundump kpool /kinetics/LacZ/ElRNAP 0 0 0 0 0 0 0 0 599.98 0 "" 5 23 1 0 0
simundump kpool /kinetics/LacZ/nucleotides 0 0 0 0 0 0 0 0 599.98 4 "" 1 23 1 \
  -2 0
simundump kreac /kinetics/LacZ/Isomerization 0 1 0 "" white 23 3 3 0
simundump kreac /kinetics/LacZ/mRNA_degradation 0 0.3 0 "" white 23 3 -1 0
simundump kpool /kinetics/LacZ/TrRNAP 0 0 0 0 0 0 0 0 599.98 0 "" 27 23 5 2 0
simundump xgraph /graphs/conc1 0 0 2100 0 98.223 0
simundump xgraph /graphs/conc2 0 0 2100 0 0.0014302 0
simundump xplot /graphs/conc1/Protein.Co 3 524288 \
  "delete_plot.w <s> <d>; edit_plot.D <w>" 7 0 0 1
simundump xplot /graphs/conc2/ElRNAP.Co 3 524288 \
  "delete_plot.w <s> <d>; edit_plot.D <w>" blue 0 0 1
simundump xplot /graphs/conc2/RBS.Co 3 524288 \
  "delete_plot.w <s> <d>; edit_plot.D <w>" 2 0 0 1
simundump xplot /graphs/conc2/RNA_pol.Co 3 524288 \
  "delete_plot.w <s> <d>; edit_plot.D <w>" 61 0 0 1
simundump xgraph /moregraphs/conc3 0 0 2100 0 1.0085 0
simundump xgraph /moregraphs/conc4 0 0 2100 0 0.030333 0
simundump xplot /moregraphs/conc3/elRIB.Co 3 524288 \
  "delete_plot.w <s> <d>; edit_plot.D <w>" 57 0 0 1
simundump xplot /moregraphs/conc4/RibRBS.Co 3 524288 \
  "delete_plot.w <s> <d>; edit_plot.D <w>" blue 0 0 1
simundump xcoredraw /edit/draw 0 -9 7 -8 6
simundump xtree /edit/draw/tree 0 \
  /kinetics/#[],/kinetics/#[]/#[],/kinetics/#[]/#[]/#[][TYPE!=proto],/kinetics/#[]/#[]/#[][TYPE!=linkinfo]/##[] \
  "edit_elm.D <v>; drag_from_edit.w <d> <S> <x> <y> <z>" auto 0.6
simundump xtext /file/notes 0 1
xtextload /file/notes \
"Based on Kierzek et al 2001 JBC 276(11):8165-8172" \
"Two special notes: The ribosome and RNA polymerase levels" \
"are buffered, and the volume is set to 1e-18 m^3." \
"This gives results comparable to, but not the same" \
"as their simulations." \
"This version is very similar to gene_exp4.g but has unbuffered" \
"the promoter conc so there is only one molecule."
addmsg /kinetics/LacZ/Ribosome_binding /kinetics/LacZ/Ribosome REAC A B 
addmsg /kinetics/LacZ/Prot_elongation /kinetics/LacZ/Ribosome REAC B A 
addmsg /kinetics/LacZ/Prot_elongation /kinetics/LacZ/Protein REAC B A 
addmsg /kinetics/LacZ/Prot_degradation /kinetics/LacZ/Protein REAC A B 
addmsg /kinetics/LacZ/Prot_degradation /kinetics/LacZ/AAs REAC B A 
addmsg /kinetics/LacZ/RBS /kinetics/LacZ/Ribosome_binding SUBSTRATE n 
addmsg /kinetics/LacZ/Ribosome /kinetics/LacZ/Ribosome_binding SUBSTRATE n 
addmsg /kinetics/LacZ/RibRBS /kinetics/LacZ/Ribosome_binding PRODUCT n 
addmsg /kinetics/LacZ/elRIB /kinetics/LacZ/Prot_elongation SUBSTRATE n 
addmsg /kinetics/LacZ/Ribosome /kinetics/LacZ/Prot_elongation PRODUCT n 
addmsg /kinetics/LacZ/Protein /kinetics/LacZ/Prot_elongation PRODUCT n 
addmsg /kinetics/LacZ/Protein /kinetics/LacZ/Prot_degradation SUBSTRATE n 
addmsg /kinetics/LacZ/AAs /kinetics/LacZ/Prot_degradation PRODUCT n 
addmsg /kinetics/LacZ/RNAPol_binding /kinetics/LacZ/RNAP REAC A B 
addmsg /kinetics/LacZ/RNASynthesis /kinetics/LacZ/RNAP REAC B A 
addmsg /kinetics/LacZ/RNASynthesis /kinetics/LacZ/RBS REAC B A 
addmsg /kinetics/LacZ/Ribosome_binding /kinetics/LacZ/RBS REAC A B 
addmsg /kinetics/LacZ/Clearance /kinetics/LacZ/RBS REAC B A 
addmsg /kinetics/LacZ/RBS_degradation /kinetics/LacZ/RBS REAC A B 
addmsg /kinetics/LacZ/Ribosome_binding /kinetics/LacZ/RibRBS REAC B A 
addmsg /kinetics/LacZ/Clearance /kinetics/LacZ/RibRBS REAC A B 
addmsg /kinetics/LacZ/Clearance /kinetics/LacZ/elRIB REAC B A 
addmsg /kinetics/LacZ/Prot_elongation /kinetics/LacZ/elRIB REAC A B 
addmsg /kinetics/LacZ/P /kinetics/LacZ/RNAPol_binding SUBSTRATE n 
addmsg /kinetics/LacZ/RNAP /kinetics/LacZ/RNAPol_binding SUBSTRATE n 
addmsg /kinetics/LacZ/P_RNAP /kinetics/LacZ/RNAPol_binding PRODUCT n 
addmsg /kinetics/LacZ/TrRNAP /kinetics/LacZ/RNASynthesis SUBSTRATE n 
addmsg /kinetics/LacZ/P /kinetics/LacZ/RNASynthesis PRODUCT n 
addmsg /kinetics/LacZ/RBS /kinetics/LacZ/RNASynthesis PRODUCT n 
addmsg /kinetics/LacZ/ElRNAP /kinetics/LacZ/RNASynthesis PRODUCT n 
addmsg /kinetics/LacZ/RNAP /kinetics/LacZ/RNASynthesis PRODUCT n 
addmsg /kinetics/LacZ/RBS /kinetics/LacZ/RBS_degradation SUBSTRATE n 
addmsg /kinetics/LacZ/nucleotides /kinetics/LacZ/RBS_degradation PRODUCT n 
addmsg /kinetics/LacZ/RibRBS /kinetics/LacZ/Clearance SUBSTRATE n 
addmsg /kinetics/LacZ/elRIB /kinetics/LacZ/Clearance PRODUCT n 
addmsg /kinetics/LacZ/RBS /kinetics/LacZ/Clearance PRODUCT n 
addmsg /kinetics/LacZ/RNAPol_binding /kinetics/LacZ/P_RNAP REAC B A 
addmsg /kinetics/LacZ/Isomerization /kinetics/LacZ/P_RNAP REAC A B 
addmsg /kinetics/LacZ/RNAPol_binding /kinetics/LacZ/P REAC A B 
addmsg /kinetics/LacZ/RNASynthesis /kinetics/LacZ/P REAC B A 
addmsg /kinetics/LacZ/RNASynthesis /kinetics/LacZ/ElRNAP REAC B A 
addmsg /kinetics/LacZ/mRNA_degradation /kinetics/LacZ/ElRNAP REAC A B 
addmsg /kinetics/LacZ/mRNA_degradation /kinetics/LacZ/nucleotides REAC B A 
addmsg /kinetics/LacZ/RBS_degradation /kinetics/LacZ/nucleotides REAC B A 
addmsg /kinetics/LacZ/P_RNAP /kinetics/LacZ/Isomerization SUBSTRATE n 
addmsg /kinetics/LacZ/TrRNAP /kinetics/LacZ/Isomerization PRODUCT n 
addmsg /kinetics/LacZ/ElRNAP /kinetics/LacZ/mRNA_degradation SUBSTRATE n 
addmsg /kinetics/LacZ/nucleotides /kinetics/LacZ/mRNA_degradation PRODUCT n 
addmsg /kinetics/LacZ/Isomerization /kinetics/LacZ/TrRNAP REAC B A 
addmsg /kinetics/LacZ/RNASynthesis /kinetics/LacZ/TrRNAP REAC A B 
addmsg /kinetics/LacZ/Protein /graphs/conc1/Protein.Co PLOT Co *Protein.Co *7 
addmsg /kinetics/LacZ/ElRNAP /graphs/conc2/ElRNAP.Co PLOT Co *ElRNAP.Co *blue 
addmsg /kinetics/LacZ/RBS /graphs/conc2/RBS.Co PLOT Co *RBS.Co *2 
addmsg /kinetics/LacZ/RNAP /graphs/conc2/RNA_pol.Co PLOT Co *RNA_pol.Co *61 
addmsg /kinetics/LacZ/elRIB /moregraphs/conc3/elRIB.Co PLOT Co *elRIB.Co *57 
addmsg /kinetics/LacZ/RibRBS /moregraphs/conc4/RibRBS.Co PLOT Co *RibRBS.Co *blue 
enddump
// End of dump

call /kinetics/LacZ/notes LOAD \
"Based on Kierzek, Zaim and Zielenkiewicz 2001 JBC 276(11):8165-8172" \
"This is NOT an exact duplicate of their model. Simulation results come" \
"out about 1/3 of their values." \
"There are two main discrepancies: they use" \
"stochastic simulations, and they also assume linear growth of the cell" \
"volume throughout the simulation. The first approximation has been" \
"tested using the stochastic simulation mode in Kinetikit, and the" \
"differences are small. The second approximation is problematic. By starting" \
"the cell at 0.5e-18 m^3, running it for half its cycle, then promoting" \
"it to full size of 1e-18 m^3 and finishing off the cycle one sees a closer" \
"match to their results for protein levels. Anyway, the purpose of this" \
"implementation is to provide a reference to the original simulation."
call /kinetics/LacZ/Ribosome/notes LOAD \
"Ribosome pool" \
"The language in the paper is a little ambiguous, but from simulation" \
"it turns out that they assume that the number of free ribosomes is " \
"held fixed at 350. In other words, buffered."
call /kinetics/LacZ/Ribosome_binding/notes LOAD \
"Equations 5 and 6 from Kierzek et al." \
"Association rate set to order of magnitude of diffusion-limited" \
"aggregation." \
"Dissociation rate set to reproduce translation initiation frequency."
call /kinetics/LacZ/Prot_elongation/notes LOAD \
"Equation 9 from Kierzek et al. They say that this step should" \
"be RibRBS-> Protein, but based on text and the logic of the synthesis," \
"it should really be ElRIB, the Ribosome elongating protein chain, that" \
"should give rise to the protein." \
"The calculation is: ribosome moves at 15 AAs /sec. The protein is 1024" \
"AAs long. So protein is formed at 0.015/sec."
call /kinetics/LacZ/Prot_degradation/notes LOAD \
"Equation 10 from Kierzek et al. Assume a half-life of 3 hours for" \
"beta-galactosidase in E coli, from " \
"Berquist and Truman 1978 Mol. Cell. Genet. 164, 105-108." \
""
call /kinetics/LacZ/RNAP/notes LOAD \
"RNA Polymerase. Kierzek et al assume mean 35 and delta = 3.5 molecules." \
"Turns out they assume that this is buffered."
call /kinetics/LacZ/RBS/notes LOAD \
"Ribosome binding site. Kierzek et al say:" \
"Based on Yarchuk et al 1992 J Mol Biol 226:581-596" \
"we have assumed the following interdependence between translation and" \
"mRNA decay: (i) RNase E and ribosomes compete for the RBS" \
"(ii) if RNase E binds to the RBS faster than the ribosome, it degrades" \
"mRNA in the 5prime to 3prime direction and does not interfere with the" \
"movement of the ribosomes that have been already bound; and " \
"(iii) Every ribosome that successfully binds to the RBS completes" \
"translation of the protein."
call /kinetics/LacZ/RibRBS/notes LOAD \
"This is the ribosome binding site protected by the bound ribosome."
call /kinetics/LacZ/elRIB/notes LOAD \
"Ribosome elongating protein chain."
call /kinetics/LacZ/RNAPol_binding/notes LOAD \
"Equations 1 and 2 from Kierzek et al." \
"Reversible RNA polymerase binding."
call /kinetics/LacZ/RNASynthesis/notes LOAD \
"Equation 4 from Kierzek et al. They say:" \
"To clear the promoter region, active RNA polymerase must move 30 to" \
"60 nucleotides (ref Record et al 1996 E coli and Salmonella 2nd ed" \
"pp 792-821 ASM Press, Washington DC)" \
"Since rate of polymerase movement is about 40 nucleotides/sec, this " \
"step takes about 1 sec. The length of the mRNA chain that is synthesized" \
"during this time corresponds roughly to the length of the leader region " \
"containing the ribosome binding site (RBS). Therefore the synthesis of" \
"the RBS and promotor clearance occur at approximately the same rate of" \
"1 per sec. .... Therefore we modeled these two processes by the single " \
"first order reaction with a rate constant of 1 per sec."
call /kinetics/LacZ/RBS_degradation/notes LOAD \
"Equation 8 from Kierzek et al, set equal to transcription initiaton" \
"frequency. This is the decay rate of unprotected RBS."
call /kinetics/LacZ/Clearance/notes LOAD \
"Equation 7 from Kierzek et al. Based on " \
"Draper , DE 1996 E coli and Salmonella 2nd Ed pp 902-908 ASM Press," \
"Washington DC. This is the rate at which the RBS is cleared."
call /kinetics/LacZ/P/notes LOAD \
"The promoter region of the gene. Assume just one gene and a single" \
"promoter on it."
call /kinetics/LacZ/ElRNAP/notes LOAD \
"Polymerase elongating a given mRNA molecule." \
"Kierzek et al assume that the RNA polymerase completes synthesis" \
"of the mRNA molecule with a rate sufficient to allow for a" \
"ribosome movement rate of 15 amino acids/sec." \
"They do not explicitly model the elongation of mRNA."
call /kinetics/LacZ/Isomerization/notes LOAD \
"Equation 3 from Kierzek et al." \
"Isomerization of closed binary complex to open binary complex."
call /kinetics/LacZ/mRNA_degradation/notes LOAD \
"Also equation 8 from Kierzek et al. Since RBS is assumed to be the rate-limiting part of" \
"the protein synthesis, we don't really need to worry about the" \
"fate of the ElRNAP. For balance we degrade it at the same rate as the" \
"RBS."
call /kinetics/LacZ/TrRNAP/notes LOAD \
"This is the Transcribing RNA Polymerase."
complete_loading