Computer-Aided Design of LIVing systEms CADLIVE automatically converts a biochemical network map to a dynamic model. JAVA application Client-Server System

Dynamic simulation by CADLIVE Very concrete model (Experimentally measured kinetics model) Very abstract model (Boolean model) INTERMEDIATE LEVEL in CADLIVE

Forward Engineering Reverse Engineering Mathematical model construction based on a biochemical network map Direct link of a network map to a math model Parameter values are tuned to reproduce biological behaviors

CADLIVE (Computer-Aided Design of LIVing systEms) A comprehensive software suite for directly connecting biochemical network maps to dynamic simulations CADLIVE Dynamic Simulator CADLIVE GUI Network Constructor CADLIVE is freely available at

Regulator-Reaction Equations Mathematical Model Simulation Biochemical Map Automatic conversion Dynamic Simulator GUI Network Constructor From a Biochemical Map to Simulation Automatic conversion

Three Layers and Two Stages

Transcription and Translation (TT) Equations Gene Layer

CMA: Conventional Mass Action Problems: Stiff Differential equations Protein Layer

GMA: General Mass Action MM Type Metabolic layer

Rapid-equilibrium approximation Binding PhaseReaction Phase DAEs are Converted from CMA By Two-Phase Partition Method (TPP)

Advantage of TPP Reducing the number of kinetic parameters Generating non-stiff DAEs

Runge-Kutta based algorithms NDF (similar to matlab ode15s) PROCESS FLOW Simulation Optimization on a GRID system Sensitivity and stability analysis

An ammonia assimilation system map The E. coli ammonia assimilation system consists of three layers: gene, protein, and metabolic layers and multiple feedback loops. An Example for Automatic Simulation

Regulator-reaction equations were automatically generated. Demonstration CADLIVE GUI Network Constructor

Export to XML file Regulator-Reaction Equations written in the XML format

Automatic Conversion XML file sent to CADLIVE Simulator CADLIVE Dynamic Simulator automatically converts Regulator-Reaction Equations into a mathematical model. Client- Server System

The gene and protein layers are converted into differential and algebraic equations (DAEs) through CMA with ordinary transcription-translation equations (TT). The metabolic layer was converted into simplified Michaelis-Menten type equations (MM). Automatic Conversion

Mathematical simulation and optimization The simulated time course appears.

Conclusion The CADLIVE Simulator is demonstrated to handle gene regulatory and metabolic networks at an intermediate level without going all the way down to exact biochemical reactions.