title: PROKARYO: an illustrative and interactive computational model of the lactose operon in the bacterium Escherichia coli.
abstract: BACKGROUND
  We are creating software for agent-based simulation and visualization of bio-molecular processes in bacterial and eukaryotic cells. As a first example, we have built a 3-dimensional, interactive computer model of an Escherichia coli bacterium and its associated biomolecular processes. Our illustrative model focuses on the gene regulatory processes that control the expression of genes involved in the lactose operon. Prokaryo, our agent-based cell simulator, incorporates cellular structures, such as plasma membranes and cytoplasm, as well as elements of the molecular machinery, including RNA polymerase, messenger RNA, lactose permease, and ribosomes.
  
  
  RESULTS
  The dynamics of cellular 'agents' are defined by their rules of interaction, implemented as finite state machines. The agents are embedded within a 3-dimensional virtual environment with simulated physical and electrochemical properties. The hybrid model is driven by a combination of (1) mathematical equations (DEQs) to capture higher-scale phenomena and (2) agent-based rules to implement localized interactions among a small number of molecular elements. Consequently, our model is able to capture phenomena across multiple spatial scales, from changing concentration gradients to one-on-one molecular interactions. We use the classic gene regulatory mechanism of the lactose operon to demonstrate our model's resolution, visual presentation, and real-time interactivity. Our agent-based model expands on a sophisticated mathematical E. coli metabolism model, through which we highlight our model's scientific validity.
  
  
  CONCLUSIONS
  We believe that through illustration and interactive exploratory learning a model system like Prokaryo can enhance the general understanding and perception of biomolecular processes. Our agent-DEQ hybrid modeling approach can also be of value to conceptualize, illustrate, and--eventually--validate cell experiments in the wet lab.
authors.affiliation: Department of Computer Science, Faculty of Science, University of Calgary, 2500 University Drive NW, Calgary, T2N 1N4, Canada. afshin@invistaware.com.
authors.forename: Afshin
authors.initials: A
authors.lastname: Esmaeili
authors.affiliation: Department of Computer Science, Faculty of Science, University of Calgary, 2500 University Drive NW, Calgary, T2N 1N4, Canada. tbdaviso@ucalgary.ca.
authors.forename: Timothy
authors.initials: T
authors.lastname: Davison
authors.affiliation: Department of Computer Science, Faculty of Science, University of Calgary, 2500 University Drive NW, Calgary, T2N 1N4, Canada. agkwu@ucalgary.ca.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wu
authors.affiliation: Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, T2N 4N1, Canada. jalcanta@ucalgary.ca.
authors.forename: Joenel
authors.initials: J
authors.lastname: Alcantara
authors.affiliation: Department of Computer Science, Faculty of Science, University of Calgary, 2500 University Drive NW, Calgary, T2N 1N4, Canada. cjacob@ucalgary.ca.|Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, T2N 4N1, Canada. cjacob@ucalgary.ca.
authors.forename: Christian
authors.initials: C
authors.lastname: Jacob
mesh_terms: D000465:Algorithms; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D007763:Lac Operon / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000378:metabolism; D008954:Models, Biological; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012984:Software
chemical_list: D029968:Escherichia coli Proteins; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; C021499:lactose permease; D012321:DNA-Directed RNA Polymerases