SIMULATINGTHEGROWTHOFVIRUSES-DukeUniversity.pdfVIP

SIMULATING THE GROWTH OF VIRUSES LINGCHONG YOU AND JOHN YIN* Department of Chemical Engineering, University of Wisconsin-Madison 1415 Engineering Drive, Madison, WI 53706-1691 USA To explore how the genome of an organism defines its growth, we have developed a computer simulation for the intracellular growth of phage T7 on its E. coli host. Our simulation, which incorporates 30 years of genetic, biochemical, physiological, and biophysical data, is used here to study how the intracellular resources of the host, determined by the specific growth rate of the host, contribute toward phage development. It is also used to probe how changes in the linear organization of genetic elements on the T7 genome can affect T7 development. Further, we show how time-series trajectories of T7 mRNA and protein levels generated by the simulation may be used as raw data to test data-mining strategies, specifically, to identify partners in protein-protein interactions. Finally, we suggest how generalization of this work can lead to a knowledge-driven simulation for the growth of any virus. Introduction Because of their small size and the central role they played in setting the foundations of molecular genetics, viruses are ideal model systems to explore how minimal genomes define processes of growth and development. The genomes of most viruses, which may be composed of single- or double-stranded DNA or RNA, range from five to 200 kilobases in length and encode from five to 300 genes. For well-studied viruses such as phage lambda, phage T7, or human immunodeficiency virus (HIV-1), all genes that are essential for growth are known