COMPUTATIONAL MODELING AND SIMULATION AS ENABLERS FOR BIOLOGICAL DISCOVERY 139
5.4.2 Cell Biology and Physiology,
5.4.2.1 Cellular Modeling and Simulation Efforts
Cellular simulation requires a theoretical framework for analyzing the interactions of molecular
components, of modules made up of those components, and of systems in which such modules are
linked to carry out a variety of functions. The theoretical goal is to quantitatively organize, analyze, and
interpret complex data on cell biological processes, and experiments provide images, biochemical and
electrophysiological data on the initial concentrations, kinetic rates, and transport properties of the
molecules and cellular structures that are presumed to be the key components of a cellular event.^41 A
simulation embeds the relevant rate laws and rate constants for the biochemical transformations being
modeled. Based on these laws and parameters, the model accepts as initial conditions the initial concen-
trations, diffusion coefficients, and locations of all molecules implicated in the transformation, and
generates predictions for the concentration of all molecular species as a function of time and space.
These predictions are compared against experiment, and the differences between prediction and experi-
ment are used to further refine the model. If the system is perturbed by the addition of a ligand,
electrical stimulus, or other experimental intervention, the model should be capable of predicting
changes as well in the relevant spatiotemporal distributions of the molecules involved.
FIGURE 5.4 Results of automatic scanning for ATP binding sites in the structure of casein kinase (PDB ID 1csn)
using WebFEATURE, a freely available, Web-based server of FEATURE. The solid red dots show the prediction of
FEATURE, they correspond correctly with the true location of the ATP binding site, shown as white cloud.
SOURCE: Courtesy of Liping Wei, Nexus Genomics, Inc., and Russ Altman, Stanford University, personal commu-
nication, December 4, 2003.
(^41) A brief introduction to the rationale underlying cellular modeling can be found at the National Resource for Cell Analysis
and Modeling (http://www.nrcam.uchc.edu/applications/applications.html).