title: Simulation of the M13 life cycle I: Assembly of a genetically-structured deterministic chemical kinetic simulation.
abstract: To expand the quantitative, systems level understanding and foster the expansion of the biotechnological applications of the filamentous bacteriophage M13, we have unified the accumulated quantitative information on M13 biology into a genetically-structured, experimentally-based computational simulation of the entire phage life cycle. The deterministic chemical kinetic simulation explicitly includes the molecular details of DNA replication, mRNA transcription, protein translation and particle assembly, as well as the competing protein-protein and protein-nucleic acid interactions that control the timing and extent of phage production. The simulation reproduces the holistic behavior of M13, closely matching experimentally reported values of the intracellular levels of phage species and the timing of events in the M13 life cycle. The computational model provides a quantitative description of phage biology, highlights gaps in the present understanding of M13, and offers a framework for exploring alternative mechanisms of regulation in the context of the complete M13 life cycle.
authors.affiliation: Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Steven W
authors.initials: SW
authors.lastname: Smeal
authors.affiliation: Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Schmitt
authors.affiliation: Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Ronnie Rodrigues
authors.initials: RR
authors.lastname: Pereira
authors.affiliation: Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Ashok
authors.initials: A
authors.lastname: Prasad
authors.affiliation: Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, CO 80523, USA; Department of Chemistry, Colorado State University, Fort Collins, CO 80523, USA; School of Biomedical Engineering,Colorado State University, Fort Collins, CO 80523, USA. Electronic address: nickfisk@colostate.edu.
authors.forename: John D
authors.initials: JD
authors.lastname: Fisk
mesh_terms: D017104:Bacteriophage M13 / Q000737:chemistry / Q000235:genetics* / Q000254:growth & development* / Q000502:physiology; D003198:Computer Simulation; D004261:DNA Replication; D007700:Kinetics; D014176:Protein Biosynthesis; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
chemical_list: D014764:Viral Proteins
keywords: Computational biology; Genetically-structured simulation; M13 bacteriophage; Systems biology; Virus life cycle