: Given the information explosion accruing among the biological sciences, it is likely that, within a decade, the composition of simple living systems and the functions of every gene/protein contained therein will be understood. At that point, it may be possible, for the first time, to understand the property of life on a molecular level. Anticipating this, the goal of this proposal is to develop a methodology that uses this information to simulate the kinetics of minimal living systems at the molecular level (part I) and to apply this methodology to simulate the simplest organism, Mycoplasma genitalium (part II). The methodology will be developed using Mechanical Cells, simple hypothetical self-replicating systems with properties analogous to those of real cells. The methodology involves decomposing such systems into hierarchically organized structures and functions. These will be reorganized into mechanistic modules, collections of elementary chemical reactions (explicating the mechanism of the module) and the associated molecular components. Complete sets of modules must be autocatalytic, a required property of living systems. The ordinary differential equations corresponding to this reaction set will be generated and solved numerically. This will require simplifying and/or subdividing the system, solving the simpler system than linking. The resulting set of rate constants and copy numbers will be used in conjunction with a stochastic computer simulator to generate kinetic plots of each molecular component. The output of the simulations will be animated using 3D visualization software. Simulation and animations will be critically compared to the properties of real cells. Mechanism will be modified, corrected, and embellished as deficiencies are noted and more experimental data become available.
