public model
Model Identifier
Short description

Leloup and Goldbeter, 1998

This model was created after the article by Leloup and Goldbeter, J Biol Rhythms 1998, Vol:13(1),pp70-87, pubmedID: 9486845
A Model for Circadian Rhythms in Drosophila Incorporating the Formation of a Complex between the PER and TIM Proteins
The parameters and initial concentrations are taken to reproduce figs. 4 D,E,F in the publication.
For a simulation without light dependent degradation of TIM_pp, change the the parameter v_dT_fac to 1.
The light/dark phases length can be set using the parameter l_d .

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To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Related Publication
  • A model for circadian rhythms in Drosophila incorporating the formation of a complex between the PER and TIM proteins.
  • Leloup JC, Goldbeter A
  • Journal of biological rhythms , 2/ 1998 , Volume 13 , pages: 70-87 , PubMed ID: 9486845
  • Unité de Chronobiologie Théorique des Sciences, Faculté des Sciences, Université Libre de Bruxelles, Campus Plaine, Brussels, Belgium.
  • The authors present a model for circadian oscillations of the Period (PER) and Timeless (TIM) proteins in Drosophila. The model for the circadian clock is based on multiple phosphorylation of PER and TIM and on the negative feedback exerted by a nuclear PER-TIM complex on the transcription of the per and tim genes. Periodic behavior occurs in a large domain of parameter space in the form of limit cycle oscillations. These sustained oscillations occur in conditions corresponding to continuous darkness or to entrainment by light-dark cycles and are in good agreement with experimental observations on the temporal variations of PER and TIM and of per and tim mRNAs. Birhythmicity (coexistence of two periodic regimes) and aperiodic oscillations (chaos) occur in a restricted range of parameter values. The results are compared to the predictions of a model based on the sole regulation by PER. Both the formation of a complex between PER and TIM and protein phosphorylation are found to favor oscillatory behavior. Determining how the period depends on several key parameters allows us to test possible molecular explanations proposed for the altered period in the per(l) and per(s) mutants. The extended model further allows the construction of phase-response curves based on the light-induced triggering of TIM degradation. These curves, established as a function of both the duration and magnitude of the effect of a light pulse, match the phase-response curves obtained experimentally in the wild type and per(s) mutant of Drosophila.
Submitter of the first revision: Lukas Endler
Submitter of this revision: Lukas Endler
Modellers: Lukas Endler

Metadata information

BioModels Database MODEL0243843132
BioModels Database BIOMD0000000171
BioModels Database BIOMD0000000016
PubMed 9486845
KEGG Pathway dme04710

Curation status


Connected external resources

SBGN view in Newt Editor

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Model files

BIOMD0000000171_url.xml SBML L2V1 representation of Leloup1998_CircClock_LD 53.24 KB Preview | Download

Additional files

BIOMD0000000171-biopax2.owl Auto-generated BioPAX (Level 2) 32.54 KB Preview | Download
BIOMD0000000171-biopax3.owl Auto-generated BioPAX (Level 3) 48.85 KB Preview | Download
BIOMD0000000171.m Auto-generated Octave file 12.06 KB Preview | Download
BIOMD0000000171.pdf Auto-generated PDF file 247.35 KB Preview | Download
BIOMD0000000171.png Auto-generated Reaction graph (PNG) 117.11 KB Preview | Download
BIOMD0000000171.sci Auto-generated Scilab file 175.00 Bytes Preview | Download
BIOMD0000000171.svg Auto-generated Reaction graph (SVG) 47.74 KB Preview | Download
BIOMD0000000171.vcml Auto-generated VCML file 897.00 Bytes Preview | Download
BIOMD0000000171.xpp Auto-generated XPP file 7.92 KB Preview | Download
BIOMD0000000171_urn.xml Auto-generated SBML file with URNs 51.96 KB Preview | Download

  • Model originally submitted by : Lukas Endler
  • Submitted: May 8, 2008 5:00:58 PM
  • Last Modified: Apr 8, 2016 4:38:12 PM
  • Version: 2 public model Download this version
    • Submitted on: Apr 8, 2016 4:38:12 PM
    • Submitted by: Lukas Endler
    • With comment: Current version of Leloup1998_CircClock_LD
  • Version: 1 public model Download this version
    • Submitted on: May 8, 2008 5:00:58 PM
    • Submitted by: Lukas Endler
    • With comment: Original import of Leloup1998_CircRythm_ld

(*) You might be seeing discontinuous revisions as only public revisions are displayed here. Any private revisions unpublished model revision of this model will only be shown to the submitter and their collaborators.

: Variable used inside SBML models

Reactions Rate Parameters
=> M_T; CN v_sT*Ki_T^n/(Ki_T^n+CN^n) v_sT=1.0 nanomolperhour; n = 4.0 dimensionless; Ki_T=1.0 nanomoleperlitre
P1 => P0 V_2P*P1/(K_2P+P1)*cytoplasm K_2P=2.0 nanomoleperlitre; V_2P=1.0 nanoMperHour
CN => kd_CN*CN*nucleus kd_CN=0.01 perhour
C => CN k1*C*cytoplasm-k2*CN*nucleus k1=1.2 perhour; k2=0.2 perhour
M_T => (v_mT/(K_mT+M_T)+kd)*M_T*cytoplasm v_mT=0.7 nanoMperHour; K_mT=0.2 nanomoleperlitre; kd = 0.01 perhour
P2 => kd*P2*cytoplasm kd = 0.01 perhour
Tt = T0+T1+T2+C+CN*nucleus/cytoplasm [] []
T2 => T1 V_4T*T2/(K_4T+T2)*cytoplasm K_4T=2.0 nanomoleperlitre; V_4T=1.0 nanoMperHour
P0 => kd*P0*cytoplasm kd = 0.01 perhour
=> P0; M_P k_sP*M_P*cytoplasm k_sP=0.9 perhour
P2 + T2 => C (k3*T2*P2-k4*C)*cytoplasm k3=1.2 pernMperHour; k4=0.6 perhour
T0 => T1 V_1T*T0/(K_1T+T0)*cytoplasm K_1T=2.0 nanomoleperlitre; V_1T=8.0 nanoMperHour
P1 => kd*P1*cytoplasm kd = 0.01 perhour
Curator's comment:
(added: 08 May 2008, 14:14:39, updated: 08 May 2008, 14:14:39)
The model has been simulated using copasi 4.3(build 25) For fig 4A one parameter, v_dT_fac, has been changed to 1 and the starting point of the simulation had to be changed to +32 hours to better fit the figure in the publication.