Biology Reference
In-Depth Information
Molecular Simulation and
Systems Biology
Although we receive a relatively static view of molecular structure
from spectroscopic tools such as x-ray crystallography and nuclear
magnetic resonance (NMR), the reality is that molecules are in constant
motion at biological temperatures. Intermolecular motions, such as
the binding or unbinding of an antibody-antigen complex, have an
important role in biological processes. In addition, biomolecules are
always flexing, bending, and stretching in ways that affect their func-
tion. For example, many proteins display
allosteric
behavior in which
the binding of a ligand to some site on the protein causes the protein
to change its shape. This can result in the active site of an enzyme
becoming operational. The folding and unfolding of a protein are more
extreme examples of intramolecular motions that have a profound
impact on biological function.
One way to understand the motions of biological molecules is by
using a computer to simulate those motions explicitly. The computa-
tional techniques used to model intra- and intermolecular motions are
known as molecular simulations. Molecular simulations are a set of
computational methods that allow the modeling of the motions of
molecules. Molecular motions are coupled to the environment—other
biomolecules, cofactors, counterions, and water. A typical molecular
simulation involves simulating the motions of all of the atoms of a pro-
tein or nucleic acid along with all of the surrounding water molecules.
The simulation is carried out by calculating the forces that atoms exert
on each other and using those forces to propagate the motions of those
atoms. A single simulation cannot capture all of the possible motions
of a molecular system, but will at best achieve a statistical sampling
of the important states and motions. Some representative images from
a molecular simulation of a protein are shown in figure 3.1.
CONNECTION TO SYSTEMS BIOLOGY
In general, molecular simulations can be used in systems biology in
two ways. First, detailed simulations can be used to calculate unknown
parameters of more simplified models. For example, it is possible to
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