| Next: Output files Up: General Considerations Previous: Optimized parameters Index |
Subsections
Multiple tasks
If a DynaFit script file contains multiple [task]s referring to the same reaction mechanism, to the same set of kinetic constants, or to the same set of experimental data, the corresponding sections can be omitted in subsequent portions of the script file. This feature is most useful in determining the reaction mechanism (``model discrimination analysis''), or in sequential processing of reaction progress curves followed by the analysis of initial reaction rates.
Model discrimination analysis
Let us assume that the same set of experimental data is to be analyzed by considering several alternate reaction mechanisms. In this case, the only sections of the script file that are different in the each regression analysis are the [mechanism] and possibly [constants]. It is then sufficient to give the location of the experimental data (section [progress] or [velocity]) only once, for the first mechanism.
Example : Determining the mechanism of ``slow, tight'' enzyme inhibition
In this extended example taken from the DynaFit distribution package, the experimental data represent the change in fluorescence upon the hydrolysis of a fluorogenic peptide by the HIV protease [2]. The experimental data are fitted consecutively to four alternate mechanisms of ``slow, tight'' binding inhibition. The program then decides on the best-fit model by applying certain statistical criteria. The important feature of this script is that the sections [responses], [concentrations] and [progress] are shown only for the first mechanisms, because they information is applicable to the remaining reaction mechanisms as well.
;------------------------------------------------------ [task] data = progress task = fit model = one-step ? [mechanism] E + S ---> ES : kon ES ---> E + P : kr E + I <==> EI : kai kdi [constants] kon = 1.21325, kr = 6.07453 kai = 10 ?, kdi = 0.01 ? [responses] P = 1.20 [concentrations] S = 5.17 [progress] directory ./examples/hiv_protease/slow_tight/data extension txt delay 5 offset auto ? local file i40a | conc. I = 0.04, E = 0.03 file i40b | conc. I = 0.04, E = 0.03 ? file i60a | conc. I = 0.06, E = 0.03 ? file i60b | conc. I = 0.06, E = 0.03 ? ;------------------------------------------------------ [task] data = progress task = fit model = two-step ? [mechanism] E + S ---> ES : kon ES ---> E + P : kr E + I <==> EI : kai kdi EI <==> EJ : kij kji [constants] kon = 1.21325, kr = 6.07453 kai = 10 ? , kdi = 0.1 ? kij = 0.1 ? , kji = 0.01 ? ;------------------------------------------------------ [task] data = progress task = fit model = iso-inhib ? [mechanism] E + S <==> ES : kon kds ES ---> E + P : kr I <==> J : kij kji E + J <==> EJ : kai kdi [constants] kon = 78.0, kds = 381, kr = 6.04 kij = 20 ?, kji = 1000 kai = 100 ?, kdi = 0.001 ? ;------------------------------------------------------ [task] data = progress task = fit model = iso-enzym ? [mechanism] E + S <==> ES : kon kds ES ---> E + P : kr E <==> F : kef kfe F + I <==> FI : kai kdi [constants] kon = 78.0, kds = 381, kr = 6.04 kai = 100 ?, kdi = 0.002 ? kef = 25 ?, kfe = 1000 [end]
Varied data types
In some situations, the same reaction mechanism will be used to treat different kinds of experimental data (e.g., reaction progress curves or initial velocities). Again, in this case it is possible to avoid repetition in the script file of those sections that are shared by the multiple [task]s.
Example: Determination and subsequent fit of initial velocities
In this example taken from the DynaFit distribution package, the sections [responses] and [velocity] are listed only for the first task but not for the second.
;-----------------------------------
; Fit each progress curve separately
; to get initial velocities.
;-----------------------------------
[task]
data = progress
task = fit
model = compet
[mechanism]
E + S <===> ES : k ks
ES ---> E + P : kcat
E + I <===> EI : k ki
[constants]
k = 100, ks = 4000 ?, kcat = 15 ?
ki = 10 ?
[responses]
P = -0.0015
[concentrations]
E = 0.04
S = 100 ?
[progress]
local
directory ./examples/pepsin/data
extension txt
offset auto ?
error constant 0.00025 ; spectrometer noise
delay 5
files 1,2,3, 6,7,8, 9,10,11, 12,13
vary conc. I = 0,0,0, 1,1,1, 2,2,2, 0.5,0.5
files 14,15,16, 17,18,19, 20,21,22
vary conc. I = 0.1,0.1,0.1,0.2,0.2,0.2,0.05,0.05,0.05
files 23,24,25
vary conc. I = 0.3,0.3,0.3
[velocity]
variable I
file ./examples/pepsin/data/veloc.txt
;-----------------------------------------
; Fit initial velocities determined above.
; Skip [responses] and [velocity] section.
;-----------------------------------------
[task]
data = velocities
task = fit
model = compet
[mechanism]
E + S <===> ES : Ks dissoc.
ES ---> E + P : kcat
E + I <===> EI : Ki dissoc.
[constants]
Ks = 37.5, kcat = 15 ?
Ki = 0.1 ?
[concentrations]
E = 0.04
S = 100
[progress]
rapid equilibrium
[end]
| Next: Output files Up: General Considerations Previous: Optimized parameters Index |
Petr Kuzmic | Jul 12 2005