E-CELL: software environment for whole-cell simulation

Motivation: Genome sequencing projects and further systematic functional an alyses of complete gene sets are producing an unprecedented mass of molecul ar information for a wide range of model organisms. This provides us with a detailed account of the cell with which we may begin to build models for s imulating intracellular molecular processes to predict the dynamic behavior of living cells. Previous work in biochemical and genetic simulation has i solated well-characterized pathways for detailed analysis, but methods for building integrative models of the cell that incorporate gene regulation, m etabolism and signaling have not been established. We, therefore, were moti vated to develop a software environment for building such integrative model s based on gene sets, and running simulations to conduct experiments in sil ico. Results: E-CELL, a modelling and simulation environment for biochemical and genetic processes, has been developed. The E-CELL system allows a user to define functions of proteins, protein-protein interactions, protein-DNA int eractions, regulation of gene expressions and other features of cellular ce ll behavior by numerically integrating the differential equations described implicity in these reaction rules. The user can observe, through a compute r display, dynamic changes in concentrations of proteins, protein complexes and other chemical compounds in the cell. Using this software, we construc ted a model of a hypothetical cell with only 127 genes sufficient for trans cription, translation, energy production and phospholipid synthesis. Most o f the genes are taken from Mycoplasma genitalium, the organism having the s mallest known chromosome, whose complete 580 kb genome sequence was determi ned at TIGR in 1995. We discuss future applications of the E-CELL system wi th special respect to genome engineering. Availability: The E-CELL software is available upon request. Supplementary information: The complete list of rules of the developed cell model with kinetic parameters can be obtained via our web site at: http:// e-cell.org/. Contact: mt@sfc.keio.ac.jp.